Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to c...Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene co-delivery.PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa ration.All steps could be finished within 30 min.Such simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined treatments.In addition,the pH responsive delivery system reduced the side effects triggered by anti-PD therapy.The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.展开更多
Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several...Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several bottlenecks,including tumor heterogeneity,low immunogenicity,immunosuppressive tumor environment,and delivery obstacles,which collectively impact their clinical effectiveness.In this study,we developed nanocomposites containing positively charged melittin(MEL)and negatively charged photosensitizer indocyanine green(ICG),embedded in dissolving microneedles(MEL/ICG-HA@DMNs).This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier,targeting superficial lesions directly.Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes.After loading MEL/ICG-HA into the microneedle,MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site,inducing localized hyperthermia and successfully ablating the tumor,but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens.Moreover,the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio,enhancing the immune response.By overcoming the limitations of traditional cancer vaccines,this system ensures precise drug delivery and robust immune activation.This innovative approach holds the potential to revolutionize cancer treatment,offering a new paradigm in precision oncology.展开更多
The low temperature,high salt content,and bacterial composition of a seawater environment can induce severe infections in open wounds,thus impeding wound healing.To date,numerous wound dressings have been developed fo...The low temperature,high salt content,and bacterial composition of a seawater environment can induce severe infections in open wounds,thus impeding wound healing.To date,numerous wound dressings have been developed for injuries and various antibacterial functions.However,ordinary antibacterial strategies could not provide long-term resistance to infections and could not promote wound healing.Here,we proposed a strategy for enhancing resistance to seawater immersion wound infection by killing bacteria and delivering bacterial antigens in situ.Specifically,MXene-embedded tannin-Eu^(3+)(M@TA-Eu)particles were constructed to effectively alleviate injuries infected through seawater immersion and persistently fight infection by forming in situ bacterial vaccines and immune memory.In the particle,the platform composed of TA and Eu3+exhibited provascularization and antigen presentation effects.MXenes with near-infrared photothermal effect were introduced to kill the bacteria,promote the recruitment of antigen presentation cells,and ultimately enhance vaccination efficacy.Experimental results showed that the particles not only effectively accelerated the healing of injuries by relieving wound inflammation and inhibiting bacteria but also produced a potent vaccination by forming in situ bacterial vaccines.Therefore,the M@TA-Eu particles are novel materials for high-grade anti-infection dressing.展开更多
In situ tumor vaccines,which leverage the antigenic profile of individual tumors,have demonstrated significant potential in tumor immunotherapy.However,their efficacy is often limited by the immunosuppressive tumor mi...In situ tumor vaccines,which leverage the antigenic profile of individual tumors,have demonstrated significant potential in tumor immunotherapy.However,their efficacy is often limited by the immunosuppressive tumor microenvironment(TME)and insufficient tumor targeting.To address these challenges,we engineered in situ nanovaccines through the self-assembly of the photosensitizer indocyanine green,immune adjuvant aluminum(Al^(3+)),and hydrophilic drug zoledronic acid(ZOL).Intravenous injection of these nanovaccines led to efficient tumor accumulation,enhancing drug bioavailability and enabling the release of tumor-associated antigens via photothermal therapy.Additionally,the built-in ZOL induces polarization of tumor-associated macrophages,reversing the immunosuppressive TME.The potent antitumor immune response triggered by these nanovaccines effectively suppresses tumor growth.This study,which integrates a straightforward assembly method,substantial drug loading capacity,and promising therapeutic outcomes,introduces a novel and effective paradigm for carrier-free in situ nanovaccines in cancer treatment.展开更多
Objective: This study aims to explore the potential of an in situ tumor vaccine based on guanidine-modified oligo-chitosan in anti-tumor immunity by constructing such a vaccine, and to provide a theoretical basis for ...Objective: This study aims to explore the potential of an in situ tumor vaccine based on guanidine-modified oligo-chitosan in anti-tumor immunity by constructing such a vaccine, and to provide a theoretical basis for the development of novel tumor immunotherapy strategies. Methods: Chitosan was degraded into oligo-chitosan by cellulase method. Guanidine-modified oligo-chitosan was synthesized using dicyandiamide, and then loaded with polyinosinic acid-polycytidylic acid(PIC) and mammalian target of rapamycin(m TOR) small interfering RNA to prepare in situ tumor vaccine nanoparticles. The expression level of m TOR protein, cell invasion, and proliferation in B16F10-OVA cells treated with different components were observed.B16F10-OVA tumor-bearing mice were prepared and divided into 5 groups. Normal saline(NC), chitosan(CHI), oligo-chitosan(COS), guanidine-based modified oligo-chitosan(GBM-COS), and nanoparticles(guanidine-modified oligo-chitosan in situ tumor vaccine, GBM-COS+PIC+m TOR) were respectively injected into the tumor sites. The tumor inhibition rate, infiltration and functional changes of immune cells in tumor tissues and draining lymph nodes, and survival period of the mice were observed. Results: In the GBM-COS+PIC+m TOR group, the expression level of m TOR protein in tumor cells was downregulated, and the cell proliferation rate and invasion rate were significantly lower than those in the other four groups(P<0.05). The tumor volume inhibition rate, DC infiltration proportion, macrophage activation level, CD8+ T cell proportion, and survival time in the B16F10-OVA tumor-bearing mouse model of the GBM-COS+PIC+m TOR group were all higher than those in the other four groups(P<0.05). Conclusion: The guanidine-modified oligo-chitosan-based nanoparticles exhibited good anti-tumor activity both in vitro and in vivo, which can provide a new candidate method for novel tumor immunotherapy by inducing immunogenic cell death(ICD) and activating immune cells.展开更多
Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory respons...Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.展开更多
Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or a...Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.展开更多
In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity sca...In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity.To break this plight,a tumor-activated and optically reinforced immunoscaffold(TURN)is exploited to trigger cancer immunoediting phases regression,thus levering potent systemic antitumor immune responses.Upon response to tumoral reactive oxygen species,TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines,and thus immunosuppression falls and immunogenicity rises.Subsequently,intermittent laser irradiation-activated photothermal agents(PL)trigger abundant tumor antigens exposure,which causes immunogenicity springs and preliminary infiltration of T cells.Finally,CD137 agonists from TURN further promotes the proliferation,function,and survival of T cells for durable antitumor effects.Therefore,cancer immunoediting phases reverse and systemic antitumor immune responses occur.TURN achieves over 90%tumor growth inhibition in both primary and secondary tumor lesions,induces potent systemic immune responses,and triggers superior long-term immune memory in vivo.Taken together,TURN provides a prospective sight for ISV from the perspective of immunoediting phases.展开更多
Cancer immunotherapy comprising of immune checkpoint blockade(ICB)therapy,immune cell therapies,cancer vaccines and many others represents a profound arsenal in the fight against different types of cancers.However,the...Cancer immunotherapy comprising of immune checkpoint blockade(ICB)therapy,immune cell therapies,cancer vaccines and many others represents a profound arsenal in the fight against different types of cancers.However,their overall clinical objective response rates,particularly against most solid tumors,are still not sufficient owing to a variety of reasons including the heterogenous expression of tumor antigens,limited tumor infiltration of effector immune cells,acquired tumor immunosuppression and some other factors.In recent years,various nanomedicine strategies have been proposed to assist cancer immunotherapy via distinct mechanisms,presenting new promises in many published studies.This perspective will thus provide a brief overview regarding the development of nanomedicine platforms for improving cancer immunotherapy.展开更多
Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microen-vironments(TIMEs).To address these unfavorable TIMEs,supplementation with tumor-associated antigens and stimulat...Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microen-vironments(TIMEs).To address these unfavorable TIMEs,supplementation with tumor-associated antigens and stimulation of immune cells at target sites are indispensable for eliciting anti-tumoral immune responses.Pre-vious research has explored the induction of immunotherapy through multiple injections and implants;however,these approaches lack consideration for patient convenience and the implementation of finely tunable immune response control systems to mitigate the side effects of over-inflammatory responses,such as cytokine storms.In this context,we describe a patient-centric nano-gel-nano system capable of sustained generation of tumorassociated antigens and release of adjuvants.This is achieved through the specific delivery of drugs to cancer cells and antigens/adjuvants to immune cells over the long term,maintaining proper concentrations within the tumor site with a single injection.This system demonstrates local immunity against tumors with a single in-jection,enhances the therapeutic efficacy of immune checkpoint blockades,and induces systemic and memory T cell responses,thus minimizing systemic side effects.展开更多
基金The authors are thankful to the National Natural Science Foundation of China(Nos.51925305,51803210,51520105004,51873208,51973217 and 51833010)Jilin province science and technology development program(Nos.20200201075JC,20180414027GH)National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2018ZX09711003-012).
文摘Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene co-delivery.PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa ration.All steps could be finished within 30 min.Such simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined treatments.In addition,the pH responsive delivery system reduced the side effects triggered by anti-PD therapy.The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.
基金supported by the National Natural Science Foundation of China(Nos.82173747,82373803)the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province(No.2021TQ060944)。
文摘Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several bottlenecks,including tumor heterogeneity,low immunogenicity,immunosuppressive tumor environment,and delivery obstacles,which collectively impact their clinical effectiveness.In this study,we developed nanocomposites containing positively charged melittin(MEL)and negatively charged photosensitizer indocyanine green(ICG),embedded in dissolving microneedles(MEL/ICG-HA@DMNs).This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier,targeting superficial lesions directly.Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes.After loading MEL/ICG-HA into the microneedle,MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site,inducing localized hyperthermia and successfully ablating the tumor,but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens.Moreover,the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio,enhancing the immune response.By overcoming the limitations of traditional cancer vaccines,this system ensures precise drug delivery and robust immune activation.This innovative approach holds the potential to revolutionize cancer treatment,offering a new paradigm in precision oncology.
基金supported by the National Key Research and Development Program of China(No.2018YFC0311103)the Project of Science and Technology Innovation Cultivation for University Students of Guangdong Province(No.pdjh202010062)+6 种基金the Science and Technology Project of Guangzhou City(No.2018020100)the General Program of China Postdoctoral Science Foundation(No.2021M701599)the National Natural Science Foundation of China(No.32201083)the Science and Technology Program of Heyuan,China(No.230510171473326)the Science and Technology Program of Guangzhou,China(No.2024A03J0232)the Medical Scientific Research Foundation of Guangdong Province of China(No.A2020548)the Fundamental Research Funds for the Central Universities,China(No.21623403).
文摘The low temperature,high salt content,and bacterial composition of a seawater environment can induce severe infections in open wounds,thus impeding wound healing.To date,numerous wound dressings have been developed for injuries and various antibacterial functions.However,ordinary antibacterial strategies could not provide long-term resistance to infections and could not promote wound healing.Here,we proposed a strategy for enhancing resistance to seawater immersion wound infection by killing bacteria and delivering bacterial antigens in situ.Specifically,MXene-embedded tannin-Eu^(3+)(M@TA-Eu)particles were constructed to effectively alleviate injuries infected through seawater immersion and persistently fight infection by forming in situ bacterial vaccines and immune memory.In the particle,the platform composed of TA and Eu3+exhibited provascularization and antigen presentation effects.MXenes with near-infrared photothermal effect were introduced to kill the bacteria,promote the recruitment of antigen presentation cells,and ultimately enhance vaccination efficacy.Experimental results showed that the particles not only effectively accelerated the healing of injuries by relieving wound inflammation and inhibiting bacteria but also produced a potent vaccination by forming in situ bacterial vaccines.Therefore,the M@TA-Eu particles are novel materials for high-grade anti-infection dressing.
基金supported by Natural Science Foundation of Shandong Province(Nos.ZR2023MB081,ZR2024QB346)Shandong Traditional Chinese Medicine Technology Project(No.Q-2023127).
文摘In situ tumor vaccines,which leverage the antigenic profile of individual tumors,have demonstrated significant potential in tumor immunotherapy.However,their efficacy is often limited by the immunosuppressive tumor microenvironment(TME)and insufficient tumor targeting.To address these challenges,we engineered in situ nanovaccines through the self-assembly of the photosensitizer indocyanine green,immune adjuvant aluminum(Al^(3+)),and hydrophilic drug zoledronic acid(ZOL).Intravenous injection of these nanovaccines led to efficient tumor accumulation,enhancing drug bioavailability and enabling the release of tumor-associated antigens via photothermal therapy.Additionally,the built-in ZOL induces polarization of tumor-associated macrophages,reversing the immunosuppressive TME.The potent antitumor immune response triggered by these nanovaccines effectively suppresses tumor growth.This study,which integrates a straightforward assembly method,substantial drug loading capacity,and promising therapeutic outcomes,introduces a novel and effective paradigm for carrier-free in situ nanovaccines in cancer treatment.
文摘Objective: This study aims to explore the potential of an in situ tumor vaccine based on guanidine-modified oligo-chitosan in anti-tumor immunity by constructing such a vaccine, and to provide a theoretical basis for the development of novel tumor immunotherapy strategies. Methods: Chitosan was degraded into oligo-chitosan by cellulase method. Guanidine-modified oligo-chitosan was synthesized using dicyandiamide, and then loaded with polyinosinic acid-polycytidylic acid(PIC) and mammalian target of rapamycin(m TOR) small interfering RNA to prepare in situ tumor vaccine nanoparticles. The expression level of m TOR protein, cell invasion, and proliferation in B16F10-OVA cells treated with different components were observed.B16F10-OVA tumor-bearing mice were prepared and divided into 5 groups. Normal saline(NC), chitosan(CHI), oligo-chitosan(COS), guanidine-based modified oligo-chitosan(GBM-COS), and nanoparticles(guanidine-modified oligo-chitosan in situ tumor vaccine, GBM-COS+PIC+m TOR) were respectively injected into the tumor sites. The tumor inhibition rate, infiltration and functional changes of immune cells in tumor tissues and draining lymph nodes, and survival period of the mice were observed. Results: In the GBM-COS+PIC+m TOR group, the expression level of m TOR protein in tumor cells was downregulated, and the cell proliferation rate and invasion rate were significantly lower than those in the other four groups(P<0.05). The tumor volume inhibition rate, DC infiltration proportion, macrophage activation level, CD8+ T cell proportion, and survival time in the B16F10-OVA tumor-bearing mouse model of the GBM-COS+PIC+m TOR group were all higher than those in the other four groups(P<0.05). Conclusion: The guanidine-modified oligo-chitosan-based nanoparticles exhibited good anti-tumor activity both in vitro and in vivo, which can provide a new candidate method for novel tumor immunotherapy by inducing immunogenic cell death(ICD) and activating immune cells.
基金Ministry of Science and Technology of China,Grant/Award Number:2022YFE0110200Natural Science Foundation of Jilin Province,Grant/Award Number:20230101037JCNational Natural Science Foundation of China,Grant/Award Numbers:52203198,52025035。
文摘Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine.However,the use of TLR7/8 agonists can cause severe inflammatory responses.In this study,we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs,which are composed of aPDL1 antibody,Fc-III-4C peptide linker(Fc-linker)and poly(L-glutamic acid)-grafted-R848.Under ultrasound irradiation,antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants.The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo.This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.
基金This work was partly supported by NCI grant R01CA229818 to Garcia-Sastre A.
文摘Oncolytic viruses(OVs)are at the forefront of biologicals for cancer treatment.They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that,either as single agents or as part of combination therapies,are being evaluated in preclinical and clinical settings.As the field gains momentum,the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus,the tumor and the immune system,with the aim of rationally designing more efficient therapeutic interventions.Nowadays,the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus,but by its contribution as an immunostimulator,triggering the transformation of the immunosuppressive tumor microenvironment(TME)into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses.Here we review the immune mechanisms and host responses induced by ssRNA(-)(negative-sense single-stranded RNA)viruses as OV platforms.We focus on two ssRNA(-)OV candidates:Newcastle disease virus(NDV),an avian paramyxovirus with one of the longest histories of utilization as an OV,and influenza A(IAV)virus,a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.
基金supported by Funds of Sichuan Province for Distinguished Young Scholar(2021JDJQ0037)the National Natural Science Foundation of China(82372123)+1 种基金Central Guide Local Science and Technology Development Special Project fund(2023FRD05038)1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYYC23004).
文摘In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity.To break this plight,a tumor-activated and optically reinforced immunoscaffold(TURN)is exploited to trigger cancer immunoediting phases regression,thus levering potent systemic antitumor immune responses.Upon response to tumoral reactive oxygen species,TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines,and thus immunosuppression falls and immunogenicity rises.Subsequently,intermittent laser irradiation-activated photothermal agents(PL)trigger abundant tumor antigens exposure,which causes immunogenicity springs and preliminary infiltration of T cells.Finally,CD137 agonists from TURN further promotes the proliferation,function,and survival of T cells for durable antitumor effects.Therefore,cancer immunoediting phases reverse and systemic antitumor immune responses occur.TURN achieves over 90%tumor growth inhibition in both primary and secondary tumor lesions,induces potent systemic immune responses,and triggers superior long-term immune memory in vivo.Taken together,TURN provides a prospective sight for ISV from the perspective of immunoediting phases.
文摘Cancer immunotherapy comprising of immune checkpoint blockade(ICB)therapy,immune cell therapies,cancer vaccines and many others represents a profound arsenal in the fight against different types of cancers.However,their overall clinical objective response rates,particularly against most solid tumors,are still not sufficient owing to a variety of reasons including the heterogenous expression of tumor antigens,limited tumor infiltration of effector immune cells,acquired tumor immunosuppression and some other factors.In recent years,various nanomedicine strategies have been proposed to assist cancer immunotherapy via distinct mechanisms,presenting new promises in many published studies.This perspective will thus provide a brief overview regarding the development of nanomedicine platforms for improving cancer immunotherapy.
基金.The authors also thank M.S.Kyungwoo Lee for his illustration and Dr.Seung Ja Oh,Dr.Hong Yeol Yoon and Yuna Cheon for their fruitful discussions on this work.
文摘Current cancer immunotherapies exhibit low response rates attributed to suppressive tumor immune microen-vironments(TIMEs).To address these unfavorable TIMEs,supplementation with tumor-associated antigens and stimulation of immune cells at target sites are indispensable for eliciting anti-tumoral immune responses.Pre-vious research has explored the induction of immunotherapy through multiple injections and implants;however,these approaches lack consideration for patient convenience and the implementation of finely tunable immune response control systems to mitigate the side effects of over-inflammatory responses,such as cytokine storms.In this context,we describe a patient-centric nano-gel-nano system capable of sustained generation of tumorassociated antigens and release of adjuvants.This is achieved through the specific delivery of drugs to cancer cells and antigens/adjuvants to immune cells over the long term,maintaining proper concentrations within the tumor site with a single injection.This system demonstrates local immunity against tumors with a single in-jection,enhances the therapeutic efficacy of immune checkpoint blockades,and induces systemic and memory T cell responses,thus minimizing systemic side effects.
