Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC...Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.展开更多
Cancer vaccines aimed at expanding the pool or increasing the activity of tumor-specific T cells against malignancies is an important immunotherapy modality that has been extensively pursued in the past decades. Howev...Cancer vaccines aimed at expanding the pool or increasing the activity of tumor-specific T cells against malignancies is an important immunotherapy modality that has been extensively pursued in the past decades. However, the clinical efficacy of cancer vaccines remains modest in comparison to other immunotherapies, such as checkpoint blockade and adoptive T cell therapy. This unsatisfactory performance is likely due to the suboptimal selection of tumor antigens for vaccine and inefficient delivery platform. Recently, vaccines designed to target cancer neoantigens have shown marked promise in both preclinical and early clinical studies. However, enormous challenges need to be overcome to develop a highly efficient and safe delivery strategy for targeting cancer vaccines to professional antigen-presenting cells and eliciting optimized immune response against cancers. To meet these challenges, biomaterials, particularly biomaterials that are designed to respond to certain environmental stimuli, termed as stimuli-responsive biomaterials, are being actively developed to precisely manipulate the trafficking and release of cancer vaccines in vivo for enhanced therapeutic efficacy and safety. In this mini review, we provide a brief overview of the recent advances in applying stimuli-responsive biomaterials in enhancing non-cellular cancer vaccines while focusing on the chemistry and material design with varied responsiveness. We also discuss the present challenges and opportunities in the field and provide a perspective for future directions.展开更多
Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation throu...Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.展开更多
The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,w...The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.展开更多
Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity ...Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.展开更多
基金the National Natural Science Foundation of China(No.82102769)the 111 Project(No.B18035,China)the Fundamental of Research Funds for the Central Universities and Beijing Natural Science Foundation(No.L212054,China).
文摘Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.
基金This work was supported in part by the Foundation Pierre Mercier pour la science, ISREC Foundation with a donation from the Bateman Foundation, Swiss National Science Foundation （Project grant 315230 173243）, Novartis Foundation for medical-biological Research （17A058）, and the Ecole polytechnique federale de Lausanne （EPFL）.
文摘Cancer vaccines aimed at expanding the pool or increasing the activity of tumor-specific T cells against malignancies is an important immunotherapy modality that has been extensively pursued in the past decades. However, the clinical efficacy of cancer vaccines remains modest in comparison to other immunotherapies, such as checkpoint blockade and adoptive T cell therapy. This unsatisfactory performance is likely due to the suboptimal selection of tumor antigens for vaccine and inefficient delivery platform. Recently, vaccines designed to target cancer neoantigens have shown marked promise in both preclinical and early clinical studies. However, enormous challenges need to be overcome to develop a highly efficient and safe delivery strategy for targeting cancer vaccines to professional antigen-presenting cells and eliciting optimized immune response against cancers. To meet these challenges, biomaterials, particularly biomaterials that are designed to respond to certain environmental stimuli, termed as stimuli-responsive biomaterials, are being actively developed to precisely manipulate the trafficking and release of cancer vaccines in vivo for enhanced therapeutic efficacy and safety. In this mini review, we provide a brief overview of the recent advances in applying stimuli-responsive biomaterials in enhancing non-cellular cancer vaccines while focusing on the chemistry and material design with varied responsiveness. We also discuss the present challenges and opportunities in the field and provide a perspective for future directions.
基金supported by a grant from the Strategic Priority Research Program of the Chinese Academy of Sciences(no.XDA09030303).
文摘Cancer treatment is a multifaceted challenge,and therapeutic vaccines have emerged as a promising approach.The micellar preparation efficiently encapsulates antigen polypeptides and enhances antigen presentation through the major histocompatibility class I pathway,promoting cytotoxic T lymphocyte immune responses.Moreover,it enables codelivery of both antigen and adjuvant to the same target antigen-presenting cells.Combining themicellar vaccine with traditional cancer treatments(such as chemotherapy,radiotherapy,and surgery)has demonstrated improved efficacy in murine tumor models.Overall,the polyethylene glycol-phosphatidylethanolamine micelle-based vaccine presents a promising platformfor cancer therapeutic vaccines.By leveraging the strengths of various treatmentmodalities,this innovative vaccine approach holds the potential to revolutionize cancer therapy and bring new possibilities for cancer patients.
基金the support of Pharmacy Laboratory Centre and Animal Centre of Shenyang Pharmaceutical Universitysupported by the State Key Laboratory(Long-acting and Targeting Drug Delivery System)the Special Construction Project(Taishan ScholarePharmacy Specially Recruited Experts).
文摘The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.
基金supported by the National Key R&D Program of China(Nos.2019YFA0904200 and 2018YFA0507600)Tsinghua University Spring Breeze Fund(No.2020Z99CFY042)the National Natural Science Foundation of China(No.92053108).
文摘Immunostimulatory therapies based on pattern recognition receptors(PRRs)have emerged as an effective approach in the fight against cancer,with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment.The agonist cyclic dinucleotides(CDNs)of the stimulator of interferon gene(STING)are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity.However,the tumor immune efficacy of CDNs is limited by several factors,including relatively narrow cytokine production,inefficient delivery to STING,and rapid clearance.In addition,a single adjuvant molecule is unable to elicit a broad cytokine response and thus cannot further amplify the anticancer effect.To address this problem,two or more agonist molecules are often used together to synergistically enhance immune efficacy.In this work,we found that a combination of the STING agonist CDGSF and the Toll-like receptor 7/8(TLR7/8)agonist 522 produced a broader cytokine response.Subsequently,we developed multicomponent nanovaccines(MCNVs)consisting of a PC7A polymer as a nanocarrier encapsulating the antigen OVA and adjuvant molecules.These MCNVs activate bone marrow-derived dendritic cells(BMDCs)to produce multiple proinflammatory factors that promote antigen cross-presentation to stimulate specific antitumor Tcell responses.In in vivo experiments,we observed that MCNVs triggered a strong T-cell response in tumor-infiltrating lymphocytes,resulting in significant tumor regression and,notably,a 100%survival rate in mice through 25 days without other partnering therapies.These data suggest that our nanovaccines have great potential to advance cancer immunotherapy with increased durability and potency.
