Hepatocellular carcinoma(HCC)is a systemic disease with augmented malignant degree,high mortality and poor prognosis.Since the establishment of the immune mechanism of tumor therapy,people have realized that immunothe...Hepatocellular carcinoma(HCC)is a systemic disease with augmented malignant degree,high mortality and poor prognosis.Since the establishment of the immune mechanism of tumor therapy,people have realized that immunotherapy is an effective means for improvement of HCC patient prognosis.Oncolytic virus is a novel immunotherapy drug,which kills tumor cells and exempts normal cells by directly lysing tumor and inducing anti-tumor immune response,and it has been extensively examined as an HCC therapy.This editorial discusses oncolytic viruses for the treatment of HCC,emphasizing viral immunotherapy strategies and clinical applications related to HCC.展开更多
In this paper,we consider oncolytic M1 cancer virotherapy reaction–diffusion model for its numerical simulation.The Galerkin finite element method(FEM)based on cubic B-splines is setup to obtain numerical solutions o...In this paper,we consider oncolytic M1 cancer virotherapy reaction–diffusion model for its numerical simulation.The Galerkin finite element method(FEM)based on cubic B-splines is setup to obtain numerical solutions of this nonlinear model.Stability of the corresponding linearized scheme is studied by the von Neumann method.Since the problem is nonlinear and its exact solutions are not available in the literature,obtained solutions are compared with the numerical solutions available in the literature.The proposed method is consistent and reliable to simulate oncolytic M1 cancer virotherapy reaction–diffusion model.展开更多
Oncolytic viral immunotherapy is gaining considerable prominence in the realm of chronic diseases treatment and rehabilitation.Oncolytic viral therapy is an intriguing therapeutic approach due to its low toxicity and ...Oncolytic viral immunotherapy is gaining considerable prominence in the realm of chronic diseases treatment and rehabilitation.Oncolytic viral therapy is an intriguing therapeutic approach due to its low toxicity and dual function of immune stimulations.This work aims to design a soft computing approach using stupendous knacks of neural networks(NNs)optimized with Bayesian regularization(BR),i.e.NNs-BR,procedure.The constructed NNs-BR technique is exploited in order to determine the approximate numerical treatment of the nonlinear multi-delayed tumor virotherapy(TVT)models in terms of the dynamic interactions between the tumor cells free of viruses,tumor cells infected by viruses,viruses,and cytotoxic T-lymphocytes(CTLs).The strength of state-of-the-art numerical approach is incorporated to develop the reference dataset for the variation in the infection rate for tumor cells,virus-free tumor cell clearance rate by CTLs,CTLs clearance rate for infectious tumor cells,the natural lifecycle of infectious tumor cells,the natural lifecycle of viral cell,the natural lifecycle of CTLs cells,tumor cells free of viruses'maximum proliferation rate,production of tumor cells with an infection,CTLs simulated ratio for infectious tumor cells,CTLs simulated ratios for virus-free cells and delay in time.The dataset is randomly chosen/segmented for training-testing-validation samples to construct the NNs models optimized with backpropagated BR representing the approximate numerical solutions of the dynamic interactions in the TVT model.The performance of the designed NNs-BR technique is accessed/evaluated and outcomes are found in good agreement with the reference solutions having the range of accuracy from 10^(-9) to 10^(-16).The eficacy of NNs-BR paradigm is further substantiated after rigorous analysis on regression metrics,learning curves on MSE,and error histograms for the dynamics of TVT model.展开更多
Liver cancer is the fifth most common cancer in the world,with China bearing a disproportionate burden of cases.Typically diagnosed at advanced stages,liver cancer often utilizes surgical treatments such as resection,...Liver cancer is the fifth most common cancer in the world,with China bearing a disproportionate burden of cases.Typically diagnosed at advanced stages,liver cancer often utilizes surgical treatments such as resection,transcatheter hepatic artery chemoembolization(TACE),and radiofrequency ablation.However,advancements in genetic engineering and tumor immunology have unveiled the distinct potential of targeted oncolytic virus therapy.Oncolytic virus,in particular,can selectively destroy tumor cells without harming normal cells,offering a promising avenue for liver cancer treatment through immune system activation,tumor microenvironment modulation,and other mechanisms.This review describes the mechanism of action of oncolytic viruses,the new development of several common oncolytic viruses,and the combination with traditional therapies,aiming to provide directions for the subsequent therapeutic research on hepatocellular carcinoma(HCC).展开更多
Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage le...Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.展开更多
Oncolytic virotherapy(OVT)is a promising option for cancer treatment.OVT involves selective oncolytic virus(OV)replication within cancer cells,which triggers anti-tumor responses and immunostimulation.Despite promisin...Oncolytic virotherapy(OVT)is a promising option for cancer treatment.OVT involves selective oncolytic virus(OV)replication within cancer cells,which triggers anti-tumor responses and immunostimulation.Despite promising potential,OVT faces critical challenges,including insufficient tumor-specific targeting,which results in limited tumor penetration and variability in therapeutic efficacy.These challenges are particularly pronounced in solid tumors with complex microenvironments and heterogeneous vascularization.A comprehensive research program is currently underway to develop and refine innovative delivery methods to address these issues to enhance OVT precision and efficacy.A principal area of investigation is the utilization of cellular carriers to enhance the delivery and distribution of OVs within tumor microenvironments,thereby optimizing immune system activation and maximizing anti-tumor effects.This review offers a comprehensive overview of the current strategies that are being used to enhance the delivery of OVs via cellular carriers with the goal of improving the clinical impact of OVT in cancer therapy.展开更多
In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developi...In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developing detection and treatment methods should continue.The diagnostic path typically begins with learning the medical history of a patient;this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy.Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization.Thus,there is a need for novel cancer detection methods such as liquid biopsy,elastography,synthetic biosensors,fluorescence imaging,and reflectance confocal microscopy.Conventional therapeutic methods,although still common in clinical practice,pose many limitations and are unsatisfactory.Nowadays,there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy,exosome-based therapy,nanotechnology,dendritic cells,chimeric antigen receptors,immune checkpoint inhibitors,natural product-based therapy,tumor-treating fields,and photodynamic therapy.The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions.As evidenced,modern methods are not without drawbacks;there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity,specificity,safety,and efficacy.Nevertheless,an appropriate route has been taken,as confirmed by the approval of some modern methods by the Food and Drug Administration.展开更多
Objective: To evaluate the therapeutic efficacy of replicative adenovirus CNHK500 in the treatment of hepatocellular carcinoma. Methods: Virus proliferation assay, cell viability assay and Western blot were performed ...Objective: To evaluate the therapeutic efficacy of replicative adenovirus CNHK500 in the treatment of hepatocellular carcinoma. Methods: Virus proliferation assay, cell viability assay and Western blot were performed to assess the selective replication and cytolysis of CNHK500 in telomerase positive liver cancer cells Hep3B, HepGII, SMMC7721 and in normal cells. Results: The replicative multiples of CNHK500 in HepGII, Hep3B and SMMC7221 after 96 h of virus proliferation were 52 000, 396 984.9 and 632 911.3 fold respectively, similar to those of wtAd5. However, CNHK500 demonstrated more significant attenuated replicative ability in normal cell lines than wtAd5. CNHK500 replicated only 3.1-100 fold at 96 h, while the wtAd5 still reached 3160-17 357 fold. CNHK500 could cause half of HepGII cells death within 7 days at MOI 2, in Hep3B cell lines the IC50 was as low as MOI 0.01, whereas the IC50 in BJ cell was as high as MOI 1000. CNHK500 E1A protein could only be detected in hepatocellular cancer cells but not in normal cells under normoxia. E1B protein could only be detected under hypoxia condition at a MOI of 1. Conclusion: CNHK500 can efficiently replicate in and kill liver cancer cells as well as wtAd5 do while it is severely attenuated in proliferation and cytolysis among normal cells. It would be a prominsing strategy for liver cancer tratment.展开更多
Objective： To evaluate the tumor selectivity and therapeutic efficiency of replication-competent adenovirus CNHK300 on human breast cancer cells. Methods： RT-PCR was used to detect the hTERT mRNA activity in various...Objective： To evaluate the tumor selectivity and therapeutic efficiency of replication-competent adenovirus CNHK300 on human breast cancer cells. Methods： RT-PCR was used to detect the hTERT mRNA activity in various breast cancer and normal fibroblast cell lines. Virus proliferation assay, cell viability assay and Western blot were applied to evaluate the proliferation and cytolysis selectivity of CNHK300. Results： The telomerase activity of MCF-7, BT-549 and SK-BR-3 was positive, while telomerase in MRC-5 and BJ was negative. The progeny virus titers in MCF-7, BT-549 and SK-BR-3 after 48 h of CNHK300 exposure was 40 625, 1 265 and 20 000 fold higher than those of 0 h, even slightly higher than those of wtAd5 （except in SK-BR-3）. ONYX-015 virus proliferation ability was weaker than that of CNHK300 in cancer cells. However, CNHK300 exhibited attenuated replicative ability as compared with wtAd5 in MRC-5 and BJ. The CNHK300 replicatative multiple was 63 and 192 fold at 48 h respectively, while the wtAd5 still multiplied 3 160-4 846 fold. CNHK300 could cause about half of breast cancer cells to die within 7 days at MOI 10 pfu/cell and below, whereas the IC50 in BJ and MRC-5 was as high as MOI 100 pfu/cell. CNHK300 E1A protein could be detected in breast cancer cells and 293 cells but not in normal fibroblast cells. Conclusion： hTERT promoter can successfully modulate the CNHK300 to be selectively replicated in breast cancer cells positive for telomerase, which may be a potential treatment strategy in breast cancer.展开更多
AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellul...AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.展开更多
Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged surviva...Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.展开更多
Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular ...Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer, including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy. This review provides an update of the new developments in cancer gene therapy, new principles, techniques, strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.展开更多
AIM： To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepat...AIM： To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma （HCC）. METHODS： CNHK500-p53 was constructed by using human telomerase reverse transcriptase （hTERT） promoter to drive adenovirus E1a gene and hypoxia response element （HRE） promoter to drive adenovirus E1b gene. p53 gene expressing cassette was inserted into the genome of replicative virus. Viral replication experiments, cytopathic effect （CPE） and methyl thiazolyl tetrazolium （MTT） assay were performed to test the selective replication and oncolytic efficacy of CNHK500-p53. RESULTS： Immunohistochemistry verified that infection with CNHK500-p53 was associated with selective replication of adenovirus and production of p53 protein in telomerase-positive and hypoxia-inducible factordependent HCC cells, p53 protein secreted from HepG2, infected with CNHK500-p53 was significantly higher than that infected with nonreplicative adenovirus Ad-p53 in vitro （388 ± 34.6 μg/L vs 76.3 ± 13.17 μg/L）. Viral replication experiments showed that replication of CNHK500-p53 and CNHK500 or WtAd5, was much stronger than that of Ad-p53 in tested HCC cell lines. CPE and H1-F assay indicated that CNHK500-p53 selectively replicated in and killed HCC cells while leaving normal cells unaffected. CONCLUSION： A more efficient gene-viral system is developed by combining selective oncolysis with exogenous expression of p53 against HCC cells.展开更多
Pancreatic cancer is one of the highest and in fact,unchanged mortality-associated tumor,with an exceptionally low survival rate due to its challenging diagnostic approach.So far,its treatment is based on a combinatio...Pancreatic cancer is one of the highest and in fact,unchanged mortality-associated tumor,with an exceptionally low survival rate due to its challenging diagnostic approach.So far,its treatment is based on a combination of approaches(such as surgical resection with or rarely without chemotherapeutic agents),but with finite limits.Thus,looking for additional space to improve pancreatic tumorigenesis therapeutic approach,research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease,but also for its early stages.In vivo gene delivery viral vectors,despite few disadvantages(possible immunogenicity,toxicity,mutagenicity,or high cost),could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems(ex vivo delivery strategies).Their dominance consists of simple preparation,easy operation and a wide range of functions.Adenoviruses are one of the most common used vectors,inducing strong immune as well as inflammatory reactions.Oncolytic virotherapy,using the above mentioned in vivo viral vectors,is one of the most promising nonpathogenic,highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect.There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems(e.g.,clustered regularly interspaced palindromic repeats-Cas9),RNA interference technology(e.g.,microRNAs,short hairpin RNA or small interfering RNA),adoptive immunotherapy and vaccination(e.g.,chimeric antigen receptor T-cell therapy)with encouraging results.展开更多
Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microen...Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.展开更多
Objective： Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK...Objective： Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods： We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results： In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion： We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.展开更多
Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant </span><span style="font-family:Verdana;">progres...Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant </span><span style="font-family:Verdana;">progress has been made in developing targeted therapies for breast cancer,</span> <span style="font-family:Verdana;">advanced breast cancer continues to have high mortality, with poor 5-year</span> <span style="font-family:Verdana;">survival rates. Thus, current therapies are insufficient in treating advanced</span><span style="font-family:Verdana;"> stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber </span><span style="font-family:Verdana;">to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We</span> <span style="font-family:Verdana;">showed that the modified virus targets and infects CXCR4- and CXCR7-</span><span style="font-family:Verdana;">overexpressing breast cancer cells more efficiently than a wild-type control</span><span style="font-family:Verdana;"> vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.展开更多
In humans colorectal cancer (CRC) is a significant cause of morbidity and mortality. New treatment options are urgently needed to supplement existing therapies. Replication-competent oncolytic viruses (RCOVs) for the ...In humans colorectal cancer (CRC) is a significant cause of morbidity and mortality. New treatment options are urgently needed to supplement existing therapies. Replication-competent oncolytic viruses (RCOVs) for the treatment of cancerous tumors?in vivo?is a relatively new therapeutic modality with great but largely unrealized potential against CRC. In the context of oncolytic virus safety, oncoselectivity is an important criterion. It is at the conceptual intersection of viral replication strategy and tumor cell biology that RCOVs acquire their oncoselectivity, and thus their safety. Every aspect of tumor molecular biology which distinguishes it from normal, non-neoplastic cells is a potential target for exploitation. In the first section of this review we will provide an explanation of some of the successful and widely used strategies for improving oncoselectivity in wild-type viruses to make them more suitable as RCOVs. In the second section we will describe some of the characteristics of CRC biology which can be exploited to provide oncoselectivity against CRC. Throughout the review examples of successfully-engineered RCOVs which embody the approach or strategy under discussion are noted. By showing what has been done, we hope to highlight what is possible and what remains to be done to generate oncoselective RCOVs for use against CRC in humans.展开更多
In this paper,we investigate the mathematical analysis of a mathematical model describing the virotherapy treatment of a cancer with logistic growth and the effect of viral cycle presented by a time delay.The cancer p...In this paper,we investigate the mathematical analysis of a mathematical model describing the virotherapy treatment of a cancer with logistic growth and the effect of viral cycle presented by a time delay.The cancer population size is divided into uninfected and infected compartments.Depending on time delay,we prove the positivity and boundedness and the stability of equilibria.We give conditions on which the viral cycle leads to“Jeff’s phenomenon”observed in laboratory and causes oscillations in cancer size via Hopf bifurcation theory.We establish an algorithm that determines the bifurcation elements via center manifold and normal form theories.We give conditions which lead to a supercritical or subcritical bifurcation.We end with numerical simulations illustrating our theoretical results.展开更多
Oncolytic virotherapy is a promising therapeutic approach treating tumors,where oncolytic viruses(OVs)can selectively infect and lyse tumor cells through replication,while also triggering long-lasting anti-tumor immun...Oncolytic virotherapy is a promising therapeutic approach treating tumors,where oncolytic viruses(OVs)can selectively infect and lyse tumor cells through replication,while also triggering long-lasting anti-tumor immune responses.Vaccinia virus(VV)has emerged as a leading candidate for use as an OV due to its broad cytophilicity and robust capacity to express exogenous genes.Consequently,oncolytic vaccinia virus(OVV)has entered clinical trials.This review provides an overview of the key strategies used in the development of OVV,summarizes the findings from clinical trials,and addresses the challenges that must be overcome in the advancement of OVV-based therapies.Furthermore,it explores potential future strategies for enhancing the development and clinical application of OVV,intending to improve tumor treatment outcomes.The review aims to facilitate the further development and clinical adoption of OVV,thereby advancing tumor therapies.展开更多
基金Supported by the Public Welfare Technology Project of Zhejiang Province,No.LGF21H160033Zhejiang Medical Technology Plan Project,No.2021KY047Hangzhou Medical Health Science and Technology Project,No.B20220173.
文摘Hepatocellular carcinoma(HCC)is a systemic disease with augmented malignant degree,high mortality and poor prognosis.Since the establishment of the immune mechanism of tumor therapy,people have realized that immunotherapy is an effective means for improvement of HCC patient prognosis.Oncolytic virus is a novel immunotherapy drug,which kills tumor cells and exempts normal cells by directly lysing tumor and inducing anti-tumor immune response,and it has been extensively examined as an HCC therapy.This editorial discusses oncolytic viruses for the treatment of HCC,emphasizing viral immunotherapy strategies and clinical applications related to HCC.
文摘In this paper,we consider oncolytic M1 cancer virotherapy reaction–diffusion model for its numerical simulation.The Galerkin finite element method(FEM)based on cubic B-splines is setup to obtain numerical solutions of this nonlinear model.Stability of the corresponding linearized scheme is studied by the von Neumann method.Since the problem is nonlinear and its exact solutions are not available in the literature,obtained solutions are compared with the numerical solutions available in the literature.The proposed method is consistent and reliable to simulate oncolytic M1 cancer virotherapy reaction–diffusion model.
文摘Oncolytic viral immunotherapy is gaining considerable prominence in the realm of chronic diseases treatment and rehabilitation.Oncolytic viral therapy is an intriguing therapeutic approach due to its low toxicity and dual function of immune stimulations.This work aims to design a soft computing approach using stupendous knacks of neural networks(NNs)optimized with Bayesian regularization(BR),i.e.NNs-BR,procedure.The constructed NNs-BR technique is exploited in order to determine the approximate numerical treatment of the nonlinear multi-delayed tumor virotherapy(TVT)models in terms of the dynamic interactions between the tumor cells free of viruses,tumor cells infected by viruses,viruses,and cytotoxic T-lymphocytes(CTLs).The strength of state-of-the-art numerical approach is incorporated to develop the reference dataset for the variation in the infection rate for tumor cells,virus-free tumor cell clearance rate by CTLs,CTLs clearance rate for infectious tumor cells,the natural lifecycle of infectious tumor cells,the natural lifecycle of viral cell,the natural lifecycle of CTLs cells,tumor cells free of viruses'maximum proliferation rate,production of tumor cells with an infection,CTLs simulated ratio for infectious tumor cells,CTLs simulated ratios for virus-free cells and delay in time.The dataset is randomly chosen/segmented for training-testing-validation samples to construct the NNs models optimized with backpropagated BR representing the approximate numerical solutions of the dynamic interactions in the TVT model.The performance of the designed NNs-BR technique is accessed/evaluated and outcomes are found in good agreement with the reference solutions having the range of accuracy from 10^(-9) to 10^(-16).The eficacy of NNs-BR paradigm is further substantiated after rigorous analysis on regression metrics,learning curves on MSE,and error histograms for the dynamics of TVT model.
基金the National Natural Science Foundation of China(No.82204447)National Key R&D Program of China,2021YFA0909800+2 种基金the Natural Science Foundation of Guangdong Province(No.2022A1515011056)the Guangzhou Science and Technology Plan Project(Nos.2024A04J4711,and 2023A03J0200)the Guangdong Basic and Applied Basic Research Foundation(2022B1515020056)。
文摘Liver cancer is the fifth most common cancer in the world,with China bearing a disproportionate burden of cases.Typically diagnosed at advanced stages,liver cancer often utilizes surgical treatments such as resection,transcatheter hepatic artery chemoembolization(TACE),and radiofrequency ablation.However,advancements in genetic engineering and tumor immunology have unveiled the distinct potential of targeted oncolytic virus therapy.Oncolytic virus,in particular,can selectively destroy tumor cells without harming normal cells,offering a promising avenue for liver cancer treatment through immune system activation,tumor microenvironment modulation,and other mechanisms.This review describes the mechanism of action of oncolytic viruses,the new development of several common oncolytic viruses,and the combination with traditional therapies,aiming to provide directions for the subsequent therapeutic research on hepatocellular carcinoma(HCC).
基金This work was supported by the Zhejiang Provincial Natural Science Foundation of China(No.LS21H060001)the Alibaba Youth Studio Project(No.ZJU-032)the Zhejiang Province Medical and Health Science and Technology Program(Nos.2022KY1455 and 2022RC136).The funding bodies had no role in the design of the study,in collection,analysis,and interpretation of data,or in drafting the manuscript.We thank Fatima ALALIWI and Ma LING for their invaluable support and encouragement.
文摘Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.
基金supported by the National Cancer Institute(1R37CA251318-01,1R01CA248111-01A1,R01CA258477-01,R01CA278911,and R01CA288403)the CPRIT Scholar Award(RR210067).
文摘Oncolytic virotherapy(OVT)is a promising option for cancer treatment.OVT involves selective oncolytic virus(OV)replication within cancer cells,which triggers anti-tumor responses and immunostimulation.Despite promising potential,OVT faces critical challenges,including insufficient tumor-specific targeting,which results in limited tumor penetration and variability in therapeutic efficacy.These challenges are particularly pronounced in solid tumors with complex microenvironments and heterogeneous vascularization.A comprehensive research program is currently underway to develop and refine innovative delivery methods to address these issues to enhance OVT precision and efficacy.A principal area of investigation is the utilization of cellular carriers to enhance the delivery and distribution of OVs within tumor microenvironments,thereby optimizing immune system activation and maximizing anti-tumor effects.This review offers a comprehensive overview of the current strategies that are being used to enhance the delivery of OVs via cellular carriers with the goal of improving the clinical impact of OVT in cancer therapy.
文摘In accordance with the World Health Organization data,cancer remains at the forefront of fatal diseases.An upward trend in cancer incidence and mortality has been observed globally,emphasizing that efforts in developing detection and treatment methods should continue.The diagnostic path typically begins with learning the medical history of a patient;this is followed by basic blood tests and imaging tests to indicate where cancer may be located to schedule a needle biopsy.Prompt initiation of diagnosis is crucial since delayed cancer detection entails higher costs of treatment and hospitalization.Thus,there is a need for novel cancer detection methods such as liquid biopsy,elastography,synthetic biosensors,fluorescence imaging,and reflectance confocal microscopy.Conventional therapeutic methods,although still common in clinical practice,pose many limitations and are unsatisfactory.Nowadays,there is a dynamic advancement of clinical research and the development of more precise and effective methods such as oncolytic virotherapy,exosome-based therapy,nanotechnology,dendritic cells,chimeric antigen receptors,immune checkpoint inhibitors,natural product-based therapy,tumor-treating fields,and photodynamic therapy.The present paper compares available data on conventional and modern methods of cancer detection and therapy to facilitate an understanding of this rapidly advancing field and its future directions.As evidenced,modern methods are not without drawbacks;there is still a need to develop new detection strategies and therapeutic approaches to improve sensitivity,specificity,safety,and efficacy.Nevertheless,an appropriate route has been taken,as confirmed by the approval of some modern methods by the Food and Drug Administration.
基金This work is supported by International Cooperation Important Project of National Natural Science Foundation of China(No.30120160824)the State 863 High Technology R&D Project of China(No.2001AA217031).
文摘Objective: To evaluate the therapeutic efficacy of replicative adenovirus CNHK500 in the treatment of hepatocellular carcinoma. Methods: Virus proliferation assay, cell viability assay and Western blot were performed to assess the selective replication and cytolysis of CNHK500 in telomerase positive liver cancer cells Hep3B, HepGII, SMMC7721 and in normal cells. Results: The replicative multiples of CNHK500 in HepGII, Hep3B and SMMC7221 after 96 h of virus proliferation were 52 000, 396 984.9 and 632 911.3 fold respectively, similar to those of wtAd5. However, CNHK500 demonstrated more significant attenuated replicative ability in normal cell lines than wtAd5. CNHK500 replicated only 3.1-100 fold at 96 h, while the wtAd5 still reached 3160-17 357 fold. CNHK500 could cause half of HepGII cells death within 7 days at MOI 2, in Hep3B cell lines the IC50 was as low as MOI 0.01, whereas the IC50 in BJ cell was as high as MOI 1000. CNHK500 E1A protein could only be detected in hepatocellular cancer cells but not in normal cells under normoxia. E1B protein could only be detected under hypoxia condition at a MOI of 1. Conclusion: CNHK500 can efficiently replicate in and kill liver cancer cells as well as wtAd5 do while it is severely attenuated in proliferation and cytolysis among normal cells. It would be a prominsing strategy for liver cancer tratment.
基金This work was supported by International Cooperation Important Project of National Natural Sciences Foundation of China(No. 30120160824) and the State 863 High Technology R&D Project of China (No. 2001AA217031)
文摘Objective： To evaluate the tumor selectivity and therapeutic efficiency of replication-competent adenovirus CNHK300 on human breast cancer cells. Methods： RT-PCR was used to detect the hTERT mRNA activity in various breast cancer and normal fibroblast cell lines. Virus proliferation assay, cell viability assay and Western blot were applied to evaluate the proliferation and cytolysis selectivity of CNHK300. Results： The telomerase activity of MCF-7, BT-549 and SK-BR-3 was positive, while telomerase in MRC-5 and BJ was negative. The progeny virus titers in MCF-7, BT-549 and SK-BR-3 after 48 h of CNHK300 exposure was 40 625, 1 265 and 20 000 fold higher than those of 0 h, even slightly higher than those of wtAd5 （except in SK-BR-3）. ONYX-015 virus proliferation ability was weaker than that of CNHK300 in cancer cells. However, CNHK300 exhibited attenuated replicative ability as compared with wtAd5 in MRC-5 and BJ. The CNHK300 replicatative multiple was 63 and 192 fold at 48 h respectively, while the wtAd5 still multiplied 3 160-4 846 fold. CNHK300 could cause about half of breast cancer cells to die within 7 days at MOI 10 pfu/cell and below, whereas the IC50 in BJ and MRC-5 was as high as MOI 100 pfu/cell. CNHK300 E1A protein could be detected in breast cancer cells and 293 cells but not in normal fibroblast cells. Conclusion： hTERT promoter can successfully modulate the CNHK300 to be selectively replicated in breast cancer cells positive for telomerase, which may be a potential treatment strategy in breast cancer.
基金Supported by the Natural Science Foundation of China, No. 30572149 the National 863 High Technology R&D Project of China, No. 2003AA216030
文摘AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter-regulated replicativeadenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.
基金Supported by the National Natural Science Foundation of China,No.81272687the Natural Science Foundation of Zhejiang Province of China,No.LZ13H160004 and No.LY16H160056the 521 Talent Project of Zhejiang Sci-Tech University
文摘Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.
文摘Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer, including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy. This review provides an update of the new developments in cancer gene therapy, new principles, techniques, strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.
基金Supported by the Major State Basic Research Development Program (973 Program) of China, No. 2003CB515507
文摘AIM： To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma （HCC）. METHODS： CNHK500-p53 was constructed by using human telomerase reverse transcriptase （hTERT） promoter to drive adenovirus E1a gene and hypoxia response element （HRE） promoter to drive adenovirus E1b gene. p53 gene expressing cassette was inserted into the genome of replicative virus. Viral replication experiments, cytopathic effect （CPE） and methyl thiazolyl tetrazolium （MTT） assay were performed to test the selective replication and oncolytic efficacy of CNHK500-p53. RESULTS： Immunohistochemistry verified that infection with CNHK500-p53 was associated with selective replication of adenovirus and production of p53 protein in telomerase-positive and hypoxia-inducible factordependent HCC cells, p53 protein secreted from HepG2, infected with CNHK500-p53 was significantly higher than that infected with nonreplicative adenovirus Ad-p53 in vitro （388 ± 34.6 μg/L vs 76.3 ± 13.17 μg/L）. Viral replication experiments showed that replication of CNHK500-p53 and CNHK500 or WtAd5, was much stronger than that of Ad-p53 in tested HCC cell lines. CPE and H1-F assay indicated that CNHK500-p53 selectively replicated in and killed HCC cells while leaving normal cells unaffected. CONCLUSION： A more efficient gene-viral system is developed by combining selective oncolysis with exogenous expression of p53 against HCC cells.
文摘Pancreatic cancer is one of the highest and in fact,unchanged mortality-associated tumor,with an exceptionally low survival rate due to its challenging diagnostic approach.So far,its treatment is based on a combination of approaches(such as surgical resection with or rarely without chemotherapeutic agents),but with finite limits.Thus,looking for additional space to improve pancreatic tumorigenesis therapeutic approach,research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease,but also for its early stages.In vivo gene delivery viral vectors,despite few disadvantages(possible immunogenicity,toxicity,mutagenicity,or high cost),could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems(ex vivo delivery strategies).Their dominance consists of simple preparation,easy operation and a wide range of functions.Adenoviruses are one of the most common used vectors,inducing strong immune as well as inflammatory reactions.Oncolytic virotherapy,using the above mentioned in vivo viral vectors,is one of the most promising nonpathogenic,highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect.There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems(e.g.,clustered regularly interspaced palindromic repeats-Cas9),RNA interference technology(e.g.,microRNAs,short hairpin RNA or small interfering RNA),adoptive immunotherapy and vaccination(e.g.,chimeric antigen receptor T-cell therapy)with encouraging results.
基金supported by the National Natural Science Foundation of China(Grant No.81830006)the Science Technology Department of Zhejiang Province(Grant No.2021C03117).
文摘Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.
基金the National Natural Science Foundation of China (No. 30120160824)the State 863 High Technology R&D Project of China (No. 2001AA217031)
文摘Objective： Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods： We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results： In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion： We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.
文摘Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant </span><span style="font-family:Verdana;">progress has been made in developing targeted therapies for breast cancer,</span> <span style="font-family:Verdana;">advanced breast cancer continues to have high mortality, with poor 5-year</span> <span style="font-family:Verdana;">survival rates. Thus, current therapies are insufficient in treating advanced</span><span style="font-family:Verdana;"> stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber </span><span style="font-family:Verdana;">to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We</span> <span style="font-family:Verdana;">showed that the modified virus targets and infects CXCR4- and CXCR7-</span><span style="font-family:Verdana;">overexpressing breast cancer cells more efficiently than a wild-type control</span><span style="font-family:Verdana;"> vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.
文摘In humans colorectal cancer (CRC) is a significant cause of morbidity and mortality. New treatment options are urgently needed to supplement existing therapies. Replication-competent oncolytic viruses (RCOVs) for the treatment of cancerous tumors?in vivo?is a relatively new therapeutic modality with great but largely unrealized potential against CRC. In the context of oncolytic virus safety, oncoselectivity is an important criterion. It is at the conceptual intersection of viral replication strategy and tumor cell biology that RCOVs acquire their oncoselectivity, and thus their safety. Every aspect of tumor molecular biology which distinguishes it from normal, non-neoplastic cells is a potential target for exploitation. In the first section of this review we will provide an explanation of some of the successful and widely used strategies for improving oncoselectivity in wild-type viruses to make them more suitable as RCOVs. In the second section we will describe some of the characteristics of CRC biology which can be exploited to provide oncoselectivity against CRC. Throughout the review examples of successfully-engineered RCOVs which embody the approach or strategy under discussion are noted. By showing what has been done, we hope to highlight what is possible and what remains to be done to generate oncoselective RCOVs for use against CRC in humans.
文摘In this paper,we investigate the mathematical analysis of a mathematical model describing the virotherapy treatment of a cancer with logistic growth and the effect of viral cycle presented by a time delay.The cancer population size is divided into uninfected and infected compartments.Depending on time delay,we prove the positivity and boundedness and the stability of equilibria.We give conditions on which the viral cycle leads to“Jeff’s phenomenon”observed in laboratory and causes oscillations in cancer size via Hopf bifurcation theory.We establish an algorithm that determines the bifurcation elements via center manifold and normal form theories.We give conditions which lead to a supercritical or subcritical bifurcation.We end with numerical simulations illustrating our theoretical results.
文摘Oncolytic virotherapy is a promising therapeutic approach treating tumors,where oncolytic viruses(OVs)can selectively infect and lyse tumor cells through replication,while also triggering long-lasting anti-tumor immune responses.Vaccinia virus(VV)has emerged as a leading candidate for use as an OV due to its broad cytophilicity and robust capacity to express exogenous genes.Consequently,oncolytic vaccinia virus(OVV)has entered clinical trials.This review provides an overview of the key strategies used in the development of OVV,summarizes the findings from clinical trials,and addresses the challenges that must be overcome in the advancement of OVV-based therapies.Furthermore,it explores potential future strategies for enhancing the development and clinical application of OVV,intending to improve tumor treatment outcomes.The review aims to facilitate the further development and clinical adoption of OVV,thereby advancing tumor therapies.
