ABSTRACT
@#B7-H3 is an immune checkpoint molecule overexpressed on the surface of a variety of tumors, and is is an ideal target for tumor immunotherapy. In this study, nitrolated T cell epitope designed in the early stage of the laboratory was used to construct an epitope vaccine that can target immune checkpoint B7-H3. The vaccine can significantly inhibit tumor growth in the CT26 colon cancer model, and has a significant synergistic effect with the PD-L1 protein vaccine. B7-H3 vaccine can increase the proportion of CD4+ T cells in splenic T lymphocytes and the proportion of CD8+ T cells in tumor-infiltrating T lymphocytes, while reducing the proportion of suppressor Treg cells in tumor-infiltrating CD4+ T lymphocytes, which effectively improves tumor immunosuppressive microenvironment. Research results suggest that the B7-H3 epitope vaccine can be used as an effective tumor vaccine candidate molecule.
ABSTRACT
@#Using the genetic code extension technology, the immunogenic amino acid, p-nitrophenylalanine, was introduced into the universal T cell epitope and then fused with the fragment of the extracellular region of the immune checkpoint molecular CD47(19-140)to construct a vaccine targeting CD47. The CD47-NitraTh vaccine elicited high titer antibody in BALB/c mice, significantly inhibited CT26 colon cancer cells growth, and increased the ratio of spleen CD4+ T cells and CD8+ T cells. Meanwhile, it promoted the polarization of naï ve T cells to Th1 cells. Notably, CD47-NitraTh not only increased the proportion of tumour-infiltrating lymphocytes but also reduced the proportion of Treg cells in tumour tissues, which means that CD47-NitraTh vaccine can remodel the tumour immunosuppressive microenvironment. The results of this study suggested that CD47-NitraTh can be used as an effective tumour vaccine candidate.
ABSTRACT
Objective To investigate the effect of treatment with endostatin combined with siRNA targeting VEGF on rats with collagen-induced arthritis (CIA).Methods Two mg/ml bovinetype Ⅱ collagen was injected into the rat footpad to build up the animal model of CIA.The experimental animal models were treated with endostatin combined with siRNA targeting VEGF 18 days later after immunization and the treatment ended 32 day later.The efficacy was evaluated by the weight,foot and ankle volume of rats.The levels of VEGF in plasma were detected by enzyme-linked immunosorbent assay (ELISA).The VEGF distribution within synovial tissue was detected and examined by immunohistochemical technique.The pathological changes of CIA were evaluated by the pathological changes of the biopsied ankle joints.Student's t test was used to evaluate the experimental data.Results The ELISA test showed that comparing with the model group (17.5±0.3),the endostatin group (15.7±0.3) ng/L and the endostatin combined siRNA targeting VEGF group (14.7±0.5) ng/L showed a significant efficacy in the treatment of CIA in rats (P＜0.05).The endostatin group (135±27) and the endostatin combined siRNA targeting VEGF group (126±71) were different in the number of VEGF in plasma and the VEGF distribution within synovial tissue (P＜0.05),the symptoms of arthritis in these rats were reduced than the model group.Conclusion Endostatin combined siRNA targeting VEGF has good therapeutic effect on rats with CIA.