T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T...T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.展开更多
Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpo...Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being approved.Chimeric antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen heterogeneity.The lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting therapies.Our review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.展开更多
Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2...Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2,4-ditrophenyl(DNP)-modified GM3 intermediate was synthesized chemoenzymatically and conjugated to keyhole limpet hemocyanin(KLH), and the resulting bioconjugate was tested for its potential as a vaccine candidate. Mice immunological studies revealed that the DNP-modified GM3(GM3-NHDNP) analog elicited strong and rapid immune responses by recruiting anti-DNP antibodies to facilitate the targeted delivery of the vaccine construct to antigen processing cells(APCs). Moreover, the endogenously produced anti-DNP antibodies, together with the elicited antibodies against GM3-NHDNP, may synergistically promote tumor binding and cancer cell death when the cancer cell surfaces are glycoengineered to express the GM3-NHDNP antigen.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32070940 and 81991491)the China Postdoctoral Science Foundation(No.2021M700115)+2 种基金the Postdoctoral Innovation Talents Support Program(No.BX20220189,China)the Science and Technology Planning Project of Fujian Province(No.2022L3080,China)the CAMS Innovation Fund for Medical Sciences(No.2019RU022,China).
文摘T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.
文摘Malignant mesothelioma(MM)is a rare,aggressive solid tumor with limited therapeutic options and poor therapeutic response.The role of immunotherapy in MM is now well established and therapeutic options,such as checkpoint inhibitors,are increasingly being approved.Chimeric antigen receptor(CAR)-T cell therapy is successfully implemented in several hematologic cancers,but currently has inadequate effect in solid tumors,owing to several limitations,such as trafficking and infiltration,limited T cell persistence and exhaustion,the immunosuppressive TME and tumor antigen heterogeneity.The lack of uniform and universal expression of tumor-associated antigens(TAAs)on tumor cells,as well as TAA heterogeneity following tumor editing post-therapy,are issues of significant importance to CAR-T cell and associated antigen-targeting therapies.Our review discusses the concept of tumor antigen heterogeneity in MM,the consequences for CAR-T cell therapies and the strategies to overcome it.
基金supported by the National Natural Science Foundation of China (Nos. 21907038, 32000904)the Natural Science Foundation of Jiangsu Province (No. BK20200601, China)+4 种基金the National Postdoctoral Program for Innovative Talents of China (No. BX20200153)the Health and Family Planning Commission of Wuxi, China (No. Z202005)the Social Development Key Project of Jiangsu Province (No. BE2019632, China)partly supported by the 111 Project (No. 111-2-06, China)the National First-class Discipline Program of Food Science and Technology (No. JUFSTR20180101, China)。
文摘Tumor-associated carbohydrate antigens(TACAs) are attractive targets for vaccine development. In this context, we described a strategy combining artificial TACA and glycoengineering for cancer vaccine development. A 2,4-ditrophenyl(DNP)-modified GM3 intermediate was synthesized chemoenzymatically and conjugated to keyhole limpet hemocyanin(KLH), and the resulting bioconjugate was tested for its potential as a vaccine candidate. Mice immunological studies revealed that the DNP-modified GM3(GM3-NHDNP) analog elicited strong and rapid immune responses by recruiting anti-DNP antibodies to facilitate the targeted delivery of the vaccine construct to antigen processing cells(APCs). Moreover, the endogenously produced anti-DNP antibodies, together with the elicited antibodies against GM3-NHDNP, may synergistically promote tumor binding and cancer cell death when the cancer cell surfaces are glycoengineered to express the GM3-NHDNP antigen.
