Cancer remains a leading global health burden.mRNA cancer vaccines,which are propelled by their rapid development,manufacturing flexibility,and proven efficacy against infectious diseases,have emerged as a transformat...Cancer remains a leading global health burden.mRNA cancer vaccines,which are propelled by their rapid development,manufacturing flexibility,and proven efficacy against infectious diseases,have emerged as a transformative approach in cancer immunotherapy.While offering significant advantages over traditional methods,challenges related to mRNA instability and in vivo delivery efficiency persist.However,technological advancements,particularly in nanoparticle formulations such as lipid nanoparticles(LNPs),have substantially mitigated these concerns.This review comprehensively examines the mechanism of action of mRNA vaccines,focusing on their ability to encode tumor-specific antigens(TSAs),particularly neoantigens,and tumor-associated antigens(TAAs)to elicit potent anti-tumor immune responses.We critically analyzed the promising application of mRNA vaccines as monotherapies and,more significantly,in combination with immune checkpoint inhibitors,chemotherapy,adoptive cell therapies(e.g.,CAR-T),and radiation to overcome the immunosuppressive tumor microenvironment.The core of this review synthesizes compelling results from key clinical trials across various cancers(e.g.,melanoma,non-small cell lung cancer,and prostate cancer),highlighting significant outcomes such as induced neoantigen-specific T-cell responses,improved recurrence-free survival,and objective tumor regression.We also discuss the groundbreaking potential of personalized neoantigen mRNA vaccines.Current challenges,including tumor heterogeneity,optimal delivery strategies,biomarker identification,and enhancing therapeutic efficacy/safety profiles,are thoroughly evaluated alongside potential solutions.Finally,we explore future directions emphasizing next-generation approaches such as advanced nanovaccines and refined personalized platforms.This review aims to provide a timely and critical analysis of the rapidly evolving landscape of mRNA cancer vaccines,underscoring their immense potential to revolutionize cancer treatment paradigms.展开更多
Cancer vaccines have garnered significant attention in cancer immunotherapy because they trigger tumor-specific immune responses.However,their effectiveness is hindered by inefficient antigen and adjuvant delivery at ...Cancer vaccines have garnered significant attention in cancer immunotherapy because they trigger tumor-specific immune responses.However,their effectiveness is hindered by inefficient antigen and adjuvant delivery at the subcellular level,which is essential to stimulate a robust CD8^(+)T cell response.This study presents PAR/OVA,a cancer nanovaccine developed by combining imiquimod(R837)-modified polyamidoamine dendrimers with the model protein antigen ovalbumin(OVA).Within the nanovaccine,R837 is an adjuvant for the Toll-like receptor 7(TLR7)pathway and a structural component that facilitates OVA loading.In dendritic cells(DCs),the high cytoplasmic glutathione levels triggered the breakdown of PAR/OVA,releasing OVA and R837,which induced DC activation and antigen cross-presentation.Furthermore,PAR/OVA vaccination showed a protective effect and effectively inhibited B16-OVA tumor progression,indicating its potential in cancer immunotherapy.Combining this vaccine with an immune checkpoint blockade enhanced antitumor efficacy by improving the ability of cytotoxic T lymphocytes to target cancer cells within the tumor microenvironment.These findings underscore the potential of this adjuvant/antigen-delivering nanovaccine in cancer immunotherapy.展开更多
Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regul...Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha(SIRPα)on macrophages and dendritic cells(DCs).Although early enthusiasm drove broad clinical development,recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential.The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations.Clinical challenges,including anemia,thrombocytopenia,suboptimal pharmacokinetics,and limited single-agent efficacy,underscore the need to develop safer,more selective approaches.Emerging next-generation strategies,such as SIRPα-directed agents,bispecific antibodies,and conditionally active therapeutics,are designed to enhance safety and tumor selectivity and reduce systemic toxicity.In addition,spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations,including with“eat-me”signals(e.g.,calreticulin[CALR])orDNA damage response therapies(e.g.,poly(ADP-ribose)polymerase[PARP]inhibitors).Rather than signaling failure,these developments underscore the need for precision,context-specific applications,and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.展开更多
Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insuffici...Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored.To address this,the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential.Among the candidates,G0-P_(D)-Lys_(50)emerged as the most effective adjuvant through in vitro screening.When complexed with antigen ovalbumin(OVA)to form chiral nanovaccines,G0-P_(L)-Lys_(50)-OVA and G0-P_(D)-Lys_(50)-OVA exhibited similar morphology,particle size,and zeta potential.Despite these comparable physicochemical properties,G0-P_(D)Lys_(50)-OVA induced significantly stronger activation of dendritic cells(DCs).Specifically,it resulted in 1.38-and 1.34-fold increases in CD11c^(+)CD80^(+)DCs and CD11c^(+)SIINFEKL-H-2Kb^(+)DCs in lymph nodes,respectively.In the LLC-OVA cancer model,G0-P_(D)-Lys_(50)-OVA reduced tumor volume by 50%compared to its enantiomer.These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.展开更多
Immunotherapy has transformed cancer treatment,marked by the approval of numerous antibody-based drugs.However,the limitations of antibodies in pharmacokinetics including long half-lives,limited oral bioavailability a...Immunotherapy has transformed cancer treatment,marked by the approval of numerous antibody-based drugs.However,the limitations of antibodies in pharmacokinetics including long half-lives,limited oral bioavailability and immunogenicity,have prompted the pursuit of small molecule-based immunotherapy.Traditional drug discovery strategies,which focus on blocking protein activity through inhibitors,face persistent hurdles,such as reliance on accessible binding pockets,poor selectivity,and the emergence of drug resistance.Targeted protein degradation(TPD)technologies have emerged as powerful tools to address these limitations,offering significant therapeutic advantages over conventional inhibition strategies,particularly for historically "undruggable" targets.In recent years,small molecule-based protein degraders have rapidly advanced in cancer immunotherapy.In this review,we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy,including degraders targeting PD-1/PD-L1,chemokine receptors,IDO1,AhR,and others.展开更多
1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effect...1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effects.Over the past decade,a promising alternative has emerged:cancer immunotherapy,which leverages the body's immune system to identify and eradicate cancer cells[1].展开更多
Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments hav...Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments have benefited many patients,which promoted the Food and Drug Administration(FDA)approval of PD-1/PD-L1 blocking drugs.In this review,we provide a detailed introduction of five PD-1/PD-L1 blocking drugs,with indications and studies,as a valuable reference for doctors and medical investigators.Moreover,the characteristics of PD-1/PD-L1 blocking therapies,including their universality and sustainability,are discussed in this review.Furthermore,we also discuss and predict the possibility of PD-L1 as an indication marker of PD-1/PD-L1 blocking therapy for pan-cancer treatment,and the current status of combination therapies.展开更多
Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the pro...Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.展开更多
Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a deat...Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a death mode of tumor cells that can promote tumor immunity.ICD can induce strong an-titumor immune responses through the ectopic exposure of calreticulin on the plasma membrane surface and the release of the non-histone nuclear protein high-mobility group box 1(HMGB1),ATP,and in-terferon(IFN),thus activating an adaptive immune response against dead cell-associated antigens and enhancing the therapeutic effect of tumor immunotherapy.Chemotherapy,radiotherapy,photothermal therapy,magneto-thermodynamics therapy,nanopulse stimulation,and oncolytic virus therapy can all induce a strong antitumor immune response by ICD.In addition,the application of nanotechnology can precisely target drug delivery and improve the efficacy of immunotherapy.Here we introduce the basic concepts and molecular mechanisms underlying the induction of ICD.Then,we summarize and discuss the progress in the application of nanotechnology in immunotherapy to promote ICD.Finally,we attempt to define the challenges and future directions in this area to extend the benefits of ICD to a broader patient population.展开更多
Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent years.Cancer vaccines as an important branch of immunotherapy are designed for delivering tumor antigens...Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent years.Cancer vaccines as an important branch of immunotherapy are designed for delivering tumor antigens to antigen-presenting cells(APCs)to stimulate a strong immune response to against tumors,representing a potentially therapeutic and prophylactic effect with the long-term anticancer benefits.Nevertheless,the disappointing outcomes of their clinical use might be attributed to dilemma in antigen selection,immunogenicity,lymph nodes(LNs)targeting ability,lysosomal escape ability,immune evasion,etc.Nanotechnology,aiming to overcome these barriers,has been utilized in cancer vaccine development for decades.Numerous preclinical and clinical studies demonstrate positive results in nanomaterials-based cancer vaccines with considerable improvement in the vaccine efficacy.In this review,we systematically introduced the characteristics of nanovaccines and highlighted the different types of nanomaterials used for cancer vaccine design.In addition,the opportunities and challenges of the emerging nanotechnology-based cancer vaccines were discussed.展开更多
Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory d...Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.展开更多
The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel prote...The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.展开更多
Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to re...Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain,circumventing the restriction of major histocompatibility complex.This review summarized the structure/design of CAR-T cells and the evolution process this technology went through,displaying the theoretical foundation for CAR-T therapy,the marketed products and the latest preclinical and clinical research progress.Finally,we provided perspectives on this technology’s development and potential future applications,especially for treating hematological malignant and solid tumors.展开更多
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resi...Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.展开更多
Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired ...Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM)due to overexpression of programmed death ligand 1(PD-L1)on the surface of cancer cell membrane.To improve the immunotherapeutic performance of CDK4/6i,we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo.We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs),and elicited protective immune response and efficiently suppressed tumor growth in vivo.This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery,which might provide a novel insight for RNAi-based cancer immunotherapy.展开更多
The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phe...The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors.Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME.Herein,we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)prodrug for potent cancer immunotherapy.The nanogel(denoted as R848-Gel)was obtained by emulsion polymerization of HSEMA and R848 prodrug(R848-HSEMA),whose size was appropriate 100 nm.R848-Gel could be internalized by macrophages and dendritic cells in vitro,and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells.In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug.Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME.In summary,this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.展开更多
Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo ...Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I - restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer - specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96 -peptide complex induces specific immune response and the explorations for gp96 - peptide complex as a therapeutic cancer vaccine are reviewed.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than two million deaths.Underlying diseases,including cancer,are high-risk facto...The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than two million deaths.Underlying diseases,including cancer,are high-risk factors for severe COVID-19 outcomes.Angiotensin-converting enzyme 2(ACE2),as a SARS-CoV-2 host cell receptor,plays a crucial role in SARS-CoV-2 invading human cells.ACE2 also has significant associations with cancer.Recent studies showed that ACE2 was inversely correlated with the activities of multiple oncogenic pathways and tumor progression phenotypes,and was positively correlated with antitumor immune response and survival prognosis in diverse cancers,suggesting a potential protective role of ACE2 in cancer progression.Positive expression of ACE2 is also correlated with programmed death-ligand 1(PD-L1)in cancer.The positive associations of ACE2 expression with antitumor immune signatures and PD-L1 expression indicate that ACE2 expression is a positive predictor for the response to immune checkpoint inhibitors(ICIs).This was evidenced in multiple cancer cohorts treated with ICIs.Thus,ACE2 may build potential connections between COVID-19 and cancer and cancer immunotherapy.The potential connections suggest that ACE2 inhibitors may not be a good option for treating COVID-19 patients with cancer,particularly in cancer patients who are receiving immunotherapy.Furthermore,the relationships between ACE2,COVID-19,and cancer are worth confirming by more experimental and clinical data,considering that many cancer patients are at high risk for COVID-19.展开更多
Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance be...Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity.Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.In addition,bacterial derivatives,including outer membrane vesicles(OMVs)produced by bacterial secretion and nanovesicles synthesized by modification of OMVs,could enhance antitumor immunity while improving safety.This perspective discusses the unique advantages of engineered bacteria and their derivatives for immunotherapy,as well as the challenges that need to be overcome to achieve clinical translation.展开更多
文摘Cancer remains a leading global health burden.mRNA cancer vaccines,which are propelled by their rapid development,manufacturing flexibility,and proven efficacy against infectious diseases,have emerged as a transformative approach in cancer immunotherapy.While offering significant advantages over traditional methods,challenges related to mRNA instability and in vivo delivery efficiency persist.However,technological advancements,particularly in nanoparticle formulations such as lipid nanoparticles(LNPs),have substantially mitigated these concerns.This review comprehensively examines the mechanism of action of mRNA vaccines,focusing on their ability to encode tumor-specific antigens(TSAs),particularly neoantigens,and tumor-associated antigens(TAAs)to elicit potent anti-tumor immune responses.We critically analyzed the promising application of mRNA vaccines as monotherapies and,more significantly,in combination with immune checkpoint inhibitors,chemotherapy,adoptive cell therapies(e.g.,CAR-T),and radiation to overcome the immunosuppressive tumor microenvironment.The core of this review synthesizes compelling results from key clinical trials across various cancers(e.g.,melanoma,non-small cell lung cancer,and prostate cancer),highlighting significant outcomes such as induced neoantigen-specific T-cell responses,improved recurrence-free survival,and objective tumor regression.We also discuss the groundbreaking potential of personalized neoantigen mRNA vaccines.Current challenges,including tumor heterogeneity,optimal delivery strategies,biomarker identification,and enhancing therapeutic efficacy/safety profiles,are thoroughly evaluated alongside potential solutions.Finally,we explore future directions emphasizing next-generation approaches such as advanced nanovaccines and refined personalized platforms.This review aims to provide a timely and critical analysis of the rapidly evolving landscape of mRNA cancer vaccines,underscoring their immense potential to revolutionize cancer treatment paradigms.
基金supported by the Guangdong Medical Science and Technology Research Fund Project(Nos.A2022124 and B2023148)the Guangdong Provincial Administration of Traditional Chinese Medicine Research Project(No.20231222)+3 种基金the National Natural Science Foundation of China(No.52403185)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515011493)the Open Fund of Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction(No.2023B121203001)the National Famous Old Traditional Chinese Medicine Experts Inheritance Studio Construction Program of the National Administration of TCM(No.(2022)75).
文摘Cancer vaccines have garnered significant attention in cancer immunotherapy because they trigger tumor-specific immune responses.However,their effectiveness is hindered by inefficient antigen and adjuvant delivery at the subcellular level,which is essential to stimulate a robust CD8^(+)T cell response.This study presents PAR/OVA,a cancer nanovaccine developed by combining imiquimod(R837)-modified polyamidoamine dendrimers with the model protein antigen ovalbumin(OVA).Within the nanovaccine,R837 is an adjuvant for the Toll-like receptor 7(TLR7)pathway and a structural component that facilitates OVA loading.In dendritic cells(DCs),the high cytoplasmic glutathione levels triggered the breakdown of PAR/OVA,releasing OVA and R837,which induced DC activation and antigen cross-presentation.Furthermore,PAR/OVA vaccination showed a protective effect and effectively inhibited B16-OVA tumor progression,indicating its potential in cancer immunotherapy.Combining this vaccine with an immune checkpoint blockade enhanced antitumor efficacy by improving the ability of cytotoxic T lymphocytes to target cancer cells within the tumor microenvironment.These findings underscore the potential of this adjuvant/antigen-delivering nanovaccine in cancer immunotherapy.
文摘Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha(SIRPα)on macrophages and dendritic cells(DCs).Although early enthusiasm drove broad clinical development,recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential.The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations.Clinical challenges,including anemia,thrombocytopenia,suboptimal pharmacokinetics,and limited single-agent efficacy,underscore the need to develop safer,more selective approaches.Emerging next-generation strategies,such as SIRPα-directed agents,bispecific antibodies,and conditionally active therapeutics,are designed to enhance safety and tumor selectivity and reduce systemic toxicity.In addition,spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations,including with“eat-me”signals(e.g.,calreticulin[CALR])orDNA damage response therapies(e.g.,poly(ADP-ribose)polymerase[PARP]inhibitors).Rather than signaling failure,these developments underscore the need for precision,context-specific applications,and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.
基金financially supported by the National Natural Science Foundation of China(Nos.U23A20591,82472144,52273158,52273159,and W2421115)the Science and Technology Department Project of Jilin Province(No.20220204018YY)+3 种基金the Industrial Technology Research and Development Project of Jilin Province(No.2023C040-8)the Health Research Talent Special Project of Jilin Province(Nos.2023SCZ70 and 2024SCZ46)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.Y2023066)the Bethune Project of Jilin University(No.2023B01)。
文摘Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored.To address this,the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential.Among the candidates,G0-P_(D)-Lys_(50)emerged as the most effective adjuvant through in vitro screening.When complexed with antigen ovalbumin(OVA)to form chiral nanovaccines,G0-P_(L)-Lys_(50)-OVA and G0-P_(D)-Lys_(50)-OVA exhibited similar morphology,particle size,and zeta potential.Despite these comparable physicochemical properties,G0-P_(D)Lys_(50)-OVA induced significantly stronger activation of dendritic cells(DCs).Specifically,it resulted in 1.38-and 1.34-fold increases in CD11c^(+)CD80^(+)DCs and CD11c^(+)SIINFEKL-H-2Kb^(+)DCs in lymph nodes,respectively.In the LLC-OVA cancer model,G0-P_(D)-Lys_(50)-OVA reduced tumor volume by 50%compared to its enantiomer.These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.
基金supported by the National Natural Science Foundation of China(No.82173668,82373706).
文摘Immunotherapy has transformed cancer treatment,marked by the approval of numerous antibody-based drugs.However,the limitations of antibodies in pharmacokinetics including long half-lives,limited oral bioavailability and immunogenicity,have prompted the pursuit of small molecule-based immunotherapy.Traditional drug discovery strategies,which focus on blocking protein activity through inhibitors,face persistent hurdles,such as reliance on accessible binding pockets,poor selectivity,and the emergence of drug resistance.Targeted protein degradation(TPD)technologies have emerged as powerful tools to address these limitations,offering significant therapeutic advantages over conventional inhibition strategies,particularly for historically "undruggable" targets.In recent years,small molecule-based protein degraders have rapidly advanced in cancer immunotherapy.In this review,we highlight recent progress in TPD-driven small-molecule drug discovery and summarize the application of these technologies in cancer immunotherapy,including degraders targeting PD-1/PD-L1,chemokine receptors,IDO1,AhR,and others.
基金supported by Australian Centre for AI in Medical Innovation(ACAMI)funded by the Victoria State Government,National University of Singapore(NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine,NUHSRO/2021/044/Kickstart/09/LOA,and 230173-A0001)National Medical Research Council(MOH-001388-00,CG21APR1005,MOH-001500-00,and MOH-001609-00)+1 种基金Singapore Ministry of Education(MOE-000387-00 and MOET32023-0005)National Research Foundation(NRF-000352-00)。
文摘1.Introduction Cancer continues to be a major cause of global mortality rates,with conventional treatments such as chemotherapy and radiotherapy exhibiting inconsistent efficacy,high costs,and considerable side effects.Over the past decade,a promising alternative has emerged:cancer immunotherapy,which leverages the body's immune system to identify and eradicate cancer cells[1].
文摘Cancer immunotherapy has greatly advanced in recent years,and PD-1/PD-L1 blocking therapy has become a major pillar of immunotherapy.Successful clinical trials of PD-1/PD-L1 blocking therapies in cancer treatments have benefited many patients,which promoted the Food and Drug Administration(FDA)approval of PD-1/PD-L1 blocking drugs.In this review,we provide a detailed introduction of five PD-1/PD-L1 blocking drugs,with indications and studies,as a valuable reference for doctors and medical investigators.Moreover,the characteristics of PD-1/PD-L1 blocking therapies,including their universality and sustainability,are discussed in this review.Furthermore,we also discuss and predict the possibility of PD-L1 as an indication marker of PD-1/PD-L1 blocking therapy for pan-cancer treatment,and the current status of combination therapies.
基金Supported by Grants in Aid for Scientific Research (C) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
文摘Colorectal cancer(CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.
基金financially supported by National Natural Science Foundation of China[Nos.82072996(Z.Sun.),81874131(Z.Sun),51703187(Z.Xu)]National Key Research and Development Program(No.2017YFSF090107)+2 种基金the Chongqing Talent Plan for Young Top Notch Talents(No.CQYC202005029)Hubei Province Natural Science Funds for Distinguished Young Scholar[No.2017CFA062(Z.Sun)]Innovative Research Team of High-level Local Universities in Shanghai[No.ZLCX20180500(Z.Sun)].
文摘Tumor immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized the cancer field.However,the limited response of tumors to immunotherapy is a major obstacle.Tumor immunogenic cell death(ICD)is a death mode of tumor cells that can promote tumor immunity.ICD can induce strong an-titumor immune responses through the ectopic exposure of calreticulin on the plasma membrane surface and the release of the non-histone nuclear protein high-mobility group box 1(HMGB1),ATP,and in-terferon(IFN),thus activating an adaptive immune response against dead cell-associated antigens and enhancing the therapeutic effect of tumor immunotherapy.Chemotherapy,radiotherapy,photothermal therapy,magneto-thermodynamics therapy,nanopulse stimulation,and oncolytic virus therapy can all induce a strong antitumor immune response by ICD.In addition,the application of nanotechnology can precisely target drug delivery and improve the efficacy of immunotherapy.Here we introduce the basic concepts and molecular mechanisms underlying the induction of ICD.Then,we summarize and discuss the progress in the application of nanotechnology in immunotherapy to promote ICD.Finally,we attempt to define the challenges and future directions in this area to extend the benefits of ICD to a broader patient population.
基金supported by the National Science Foundation for Excellent Young Scholars(No.32122052)National Natural Science Foundation Regional Innovation and Development(No.U19A2003).
文摘Cancer immunotherapy harnesses the immune system to attack tumors and has received extensive attention in recent years.Cancer vaccines as an important branch of immunotherapy are designed for delivering tumor antigens to antigen-presenting cells(APCs)to stimulate a strong immune response to against tumors,representing a potentially therapeutic and prophylactic effect with the long-term anticancer benefits.Nevertheless,the disappointing outcomes of their clinical use might be attributed to dilemma in antigen selection,immunogenicity,lymph nodes(LNs)targeting ability,lysosomal escape ability,immune evasion,etc.Nanotechnology,aiming to overcome these barriers,has been utilized in cancer vaccine development for decades.Numerous preclinical and clinical studies demonstrate positive results in nanomaterials-based cancer vaccines with considerable improvement in the vaccine efficacy.In this review,we systematically introduced the characteristics of nanovaccines and highlighted the different types of nanomaterials used for cancer vaccine design.In addition,the opportunities and challenges of the emerging nanotechnology-based cancer vaccines were discussed.
基金supported by the National Natural Science Foundation of China(Grant Nos.62175198)the Natural Science Foundation of Fujian Province of China(Grant No.2020J02010)+1 种基金the Joint Funds for the innovation of science and Technology,Fujian province(Grant No.2019Y9046)the Fundamental Research Funds for the Central Universities(Grant No.xzy022020037).
文摘Red blood cells(RBCs)have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells,but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue.Herein,artificial RBCs(designated FTP@RBCM)with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal-organic frameworks(FTPs,as the core),including photodynamic/chemodynamic-like,catalase-like and glutathione peroxidase-like activities.Meanwhile,owing to the advantages of long circulation abilities of RBCs provided by their cell membranes(RBCMs),FTP with a surface coated with RBCMs(FTP@RBCM)could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency.Intriguingly,this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death,which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3(Tim-3)checkpoint blockade,leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors.Therefore,such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.
基金the National Key Research and Development Program of China(Grant Nos.2022YFC3401500 and 2020YFA0803201 to P.W.,and 2021YFA1302200 to L.F.)the National Natural Science Foundation of China(Grant Nos.31830053,31920103007,and 82341028 to P.W.+1 种基金82122056,82073153,and 31871398 to L.F.and 31900568 to P.W.)the Natural Science Foundation of Shanghai(Grant No.22ZR1450700 to Z.J.W.)。
文摘The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782 and 82241002)the Shanghai Science and Technology Committee(No.19430741500)+1 种基金National Innovation and Entrepreneurship Training Program for Undergraduate(No.202210316145)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(No.zdsys202103)。
文摘Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain,circumventing the restriction of major histocompatibility complex.This review summarized the structure/design of CAR-T cells and the evolution process this technology went through,displaying the theoretical foundation for CAR-T therapy,the marketed products and the latest preclinical and clinical research progress.Finally,we provided perspectives on this technology’s development and potential future applications,especially for treating hematological malignant and solid tumors.
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3401404)the National Natural Science Foundation of China(Grant Nos.32170935 and 31930066).
文摘Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.
基金financially supported by the National Natural Science Foundation of China(Nos.51873228 and 31671024)Basic Research Program of Shenzhen(No.JCYJ20180227175420974)+1 种基金Science and Technology Development Fund,Macao SAR(No.083/2017/A2)Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences。
文摘Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM)due to overexpression of programmed death ligand 1(PD-L1)on the surface of cancer cell membrane.To improve the immunotherapeutic performance of CDK4/6i,we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo.We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs),and elicited protective immune response and efficiently suppressed tumor growth in vivo.This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery,which might provide a novel insight for RNAi-based cancer immunotherapy.
基金the National Natural Science Foundation of China(Nos.51922043,52173122 and 31771091)Guangdong Provincial Program(No.2017GC010304)+1 种基金Science and Technology Planning Project of Ganzhou(No.202101074816)Fundamental Research Funds for Central Universities.
文摘The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors.Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME.Herein,we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)prodrug for potent cancer immunotherapy.The nanogel(denoted as R848-Gel)was obtained by emulsion polymerization of HSEMA and R848 prodrug(R848-HSEMA),whose size was appropriate 100 nm.R848-Gel could be internalized by macrophages and dendritic cells in vitro,and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells.In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug.Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME.In summary,this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.
基金This project was supported by the National Natural Sciences Foundation of China (No. 30171089).
文摘Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I - restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer - specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96 -peptide complex induces specific immune response and the explorations for gp96 - peptide complex as a therapeutic cancer vaccine are reviewed.
文摘The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in more than two million deaths.Underlying diseases,including cancer,are high-risk factors for severe COVID-19 outcomes.Angiotensin-converting enzyme 2(ACE2),as a SARS-CoV-2 host cell receptor,plays a crucial role in SARS-CoV-2 invading human cells.ACE2 also has significant associations with cancer.Recent studies showed that ACE2 was inversely correlated with the activities of multiple oncogenic pathways and tumor progression phenotypes,and was positively correlated with antitumor immune response and survival prognosis in diverse cancers,suggesting a potential protective role of ACE2 in cancer progression.Positive expression of ACE2 is also correlated with programmed death-ligand 1(PD-L1)in cancer.The positive associations of ACE2 expression with antitumor immune signatures and PD-L1 expression indicate that ACE2 expression is a positive predictor for the response to immune checkpoint inhibitors(ICIs).This was evidenced in multiple cancer cohorts treated with ICIs.Thus,ACE2 may build potential connections between COVID-19 and cancer and cancer immunotherapy.The potential connections suggest that ACE2 inhibitors may not be a good option for treating COVID-19 patients with cancer,particularly in cancer patients who are receiving immunotherapy.Furthermore,the relationships between ACE2,COVID-19,and cancer are worth confirming by more experimental and clinical data,considering that many cancer patients are at high risk for COVID-19.
基金supported by the National Natural Science Foundation of China(nos.82222035 and 82372106)the Shenzhen Medical Research Found(no.B2302041).
文摘Leveraging bacteria for cancer immunotherapy has gradually attracted wide attention since the discovery of“Cloey’s toxin.”However,one of the persistent challenges for bacteria-based therapy is striking a balance between safety and immunogenicity.Genetically engineered bacteria with virulence factors removed could further enhance antitumor ability by integrating genetic elements.In addition,bacterial derivatives,including outer membrane vesicles(OMVs)produced by bacterial secretion and nanovesicles synthesized by modification of OMVs,could enhance antitumor immunity while improving safety.This perspective discusses the unique advantages of engineered bacteria and their derivatives for immunotherapy,as well as the challenges that need to be overcome to achieve clinical translation.
