Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated act...Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57B1/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P〈0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD4513 was measured by real-time PCR. The results indicated that GADD45β transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/B1 mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P〈0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.展开更多
Objective THANK, known as a member of TNF superfamily, is a potent costimulator of both B and T lymphocytes and can promote astrong immune response. To investigate its role in liver immunotherapy, the anti-tumor effec...Objective THANK, known as a member of TNF superfamily, is a potent costimulator of both B and T lymphocytes and can promote astrong immune response. To investigate its role in liver immunotherapy, the anti-tumor effects of the THANK-transduced hepatoma cellline SMMU-7721 in vitro and in vivo were studied.Methods THANK full-length cDNA was transfected into SMMU-7721 cell line. The transfectant with stable expression of THANK wasobtained by clone selection and THANK s effects on hepatoma cells were analyzed, further the tumorigenicity of THANK-transduced7721 cells was examined in nude mice.Results THANK's expression in 7721 cells inhibited the growth of hepatoma cells and induced a strong CTL response in vitro. The cellcycle analysis showed that THANK transfected 7721 cells were arrested in the S phase. The expression of THANK in SMMU-7721 cellline not only inhibited the tumorigenicity of 7721 cells, but also induced a systemic immune response against re-challenge of parental7721 tumors.Conclusion THANK transduction in SMMU-7721 cells can induce an effective immune response in nude mice and may be useful for theimmunotherapy of hepatomas.展开更多
Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and su...Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and sustain concentrations of therapeutics at tumor sites. Local drug delivery systems(LDDSs) like the biomaterial scaffold-based drug delivery systems have emerged as a promising approach for delivering immunotherapeutic agents facilely and intensively in situ with reduced systemic toxicity. In this review, recent advances in biomaterial scaffold-based LDDSs for the administration of immunotherapeutic agents including vaccines, immunomodulators, and immune cells are summarized. Moreover, codelivery systems are also evaluated for local immunotherapy-involving combination anti-tumor therapy,including chemotherapy-immunotherapy, photothermal-immunotherapy, and other combination therapies. Finally, the current challenges and future perspectives on the development of next-generation LDDSs for cancer immunotherapy are discussed.展开更多
文摘Immunization with inactivated autoreactive T cells may induce idiotype anti-idiotypic reactions to deplete autoreactive T cells, which are involved in autoimmune diseases. However, it is unknown whether attenuated activated healthy autologous T-cell immunization could increase anti-tumor immune responses. To this end, C57B1/6 mice were immunized with attenuated activated autologous T cells. The splenocytes from immunized mice showed a higher proliferative ability than that from naive mice. The special phenotype analysis showed that there were more CD8+ T cells and CD62L+ T cells in immunized mice after 24 h of culture with 10% fetal calf serum complete medium in vitro (P〈0.01). These results demonstrated that this immunization may activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation-induced cell death (AICD) in vitro. To further study the relative genes that are responsible for the higher proliferation and resistance to AICD, the expression of Fas/Fas ligand (FasL) and GADD4513 was measured by real-time PCR. The results indicated that GADD45β transcription was higher in the splenocytes from immunized mice than that in the naive mice. In addition, the Fas expression showed a parallel higher, but FasL did not change obviously. To investigate the biologic functions induced by immunization in vivo, a tumor model was established by EL-4 tumor cell inoculation in C57/B1 mice. Mice receiving autologous T-cell immunization had significantly inhibited tumor growth in vivo (P〈0.01). This study implicated that immunization with attenuated activated autologous T cells enhances anti-tumor immune responses that participate in tumor growth inhibition.
文摘Objective THANK, known as a member of TNF superfamily, is a potent costimulator of both B and T lymphocytes and can promote astrong immune response. To investigate its role in liver immunotherapy, the anti-tumor effects of the THANK-transduced hepatoma cellline SMMU-7721 in vitro and in vivo were studied.Methods THANK full-length cDNA was transfected into SMMU-7721 cell line. The transfectant with stable expression of THANK wasobtained by clone selection and THANK s effects on hepatoma cells were analyzed, further the tumorigenicity of THANK-transduced7721 cells was examined in nude mice.Results THANK's expression in 7721 cells inhibited the growth of hepatoma cells and induced a strong CTL response in vitro. The cellcycle analysis showed that THANK transfected 7721 cells were arrested in the S phase. The expression of THANK in SMMU-7721 cellline not only inhibited the tumorigenicity of 7721 cells, but also induced a systemic immune response against re-challenge of parental7721 tumors.Conclusion THANK transduction in SMMU-7721 cells can induce an effective immune response in nude mice and may be useful for theimmunotherapy of hepatomas.
基金supported by the National Natural Science Foundation of China (31900945)Basic Research Program of Shenzhen(JCYJ20170412111100742, JCYJ20180507182413022)+2 种基金Fok YingTong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)Postdoctoral Science Foundation of China (2018M643175)Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003)。
文摘Immunotherapy has attracted tremendous attention due to the remarkable clinical successes for treating a broad spectrum of tumors. One challenge for cancer immunotherapy is the inability to control localization and sustain concentrations of therapeutics at tumor sites. Local drug delivery systems(LDDSs) like the biomaterial scaffold-based drug delivery systems have emerged as a promising approach for delivering immunotherapeutic agents facilely and intensively in situ with reduced systemic toxicity. In this review, recent advances in biomaterial scaffold-based LDDSs for the administration of immunotherapeutic agents including vaccines, immunomodulators, and immune cells are summarized. Moreover, codelivery systems are also evaluated for local immunotherapy-involving combination anti-tumor therapy,including chemotherapy-immunotherapy, photothermal-immunotherapy, and other combination therapies. Finally, the current challenges and future perspectives on the development of next-generation LDDSs for cancer immunotherapy are discussed.
