Immune effects of nano-tumor vaccine against melanoma in mice / 中国生物制品学杂志

@#Objective To investigate the anti-melanoma immune effects of nano-tumor vaccine based on nano-adjuvant[CpG-coated nanoparticles(CNP)] and melanoma cell lysate antigen.Methods The immunoregulatory effects of CNP and melanoma cell lysate antigens on bone marrow-derived dendritic cells(BMDCs) and the regulatory effects on expression and secretion of cytokines IL-6 and IL-12 were investigated.After the mice inoculated with melanoma cells formed tumor,40C57BL/6N fermale mice with similar size of tumor were randomly divided into 4 groups:control(PBS) group,adjuvant(CNP) group,lysate(Lysate) group and vaccine(CNP+Lysate) group,which were administered subcutaneously once a week for 3 weeks.The tumor size of mice was recorded every 3 d and the tumor growth curve was drawn.The peripheral blood of mice was collected to detect the contents of IFN_γ and TNF_α,and immunohistochemical method was used to detect the infiltration of CD8~+T lymphocytes in tumor tissues.Results Compared with PBS,CpG and tumor lysate antigen groups,nano-vaccine adjuvant CNP effectively stimulated BMDCs maturation and promoted IL-6 and IL-12 secretion;Nanotumor vaccine showed good anti-tumor activity in vivo, the tumor size of mice in vaccine group decreased significantly,and the secretion levels of IFN_γ and TNF-α in serum were significantly higher than those in other groups;The infiltration of CD8~+T lymphocytes in tumor tissues of mice in vaccine group was also significantly better than that in other groups.Conclusion Nano-tumor vaccine effectively activated BMDCs,highly expressed immune factors,and also effectively inhibited tumor growth,showing good application potential.

Photoredox Deaminative Alkylation in DNA-Encoded Library Synthesis.

Herein, we report an on-DNA photoredox-mediated deaminative alkylation method for diversifying DNA-tagged acrylamide substrate with amine-derived radicals. The radicals can be conveniently generated from sterically hindered primary amines, and the deaminative alkylation can tolerate a broad array of radical precursors. Furthermore, the methodology is applicable to Boc-protected diamines, free amino acids, and aryl halides, which bear functional groups enabling additional rounds of diversification. The method is believed to offer a high potential for constructing DNA-encoded libraries, as was demonstrated by the production of a mock library in a 2 × 3 matrix format and confirmation of DNA stability by UPLC-MS and qPCR experiments.

Co-assembled nanocomplexes of peptide neoantigen Adpgk and Toll-like receptor 9 agonist CpG ODN for efficient colorectal cancer immunotherapy.

Cancer vaccines targeting tumor specific neoantigens derived from nonsynonymous mutations of tumor cells have emerged as an effective approach to induce antitumor T cells responses for personalized cancer immunotherapy. Despite the enormous potential of synthetic peptides as a common modality for neoantigen vaccines, their practical efficacy was limited due to their relatively low immunogenicity. Herein, we modify neoantigen peptide (Adpgk) derived from MC-38 colon carcinoma by supplementing ten consecutive positively-charged lysines (10 K-Adpgk) to obtain cationic polypeptide. And then we made them self-assemble with toll-like receptor 9 (TLR-9) agonist CpG oligodeoxynucleotides (CpG ODN) adjuvant directly forming antigen/adjuvant integrated nanocomplexes (PCNPs) through electrostatic interaction for potent tumor immunotherapy. The optimal formed PCNPs were around 175 nm with uniform size distribution and could maintain stability in physiological saline solution. CpG ODN and 10 K-Adpgk in the formed PCNPs could be effectively uptake by dendritic cells (DCs) and stimulate the maturation of DCs as well as improving the efficiency of antigen cross-presentation efficiency in vitro. Furthermore, the PCNPs vaccine could markedly improve neoantigen and adjuvant co-delivery efficiency to lymphoid organs and activate cytotoxic T cells. In addition, vaccination with PCNPs could not only offer prophylactic to protect mice from challenged MC-38 colorectal tumors, but also achieve a better anti-tumor effect in an established colorectal tumor model, and significantly prolong the survival rate of tumor-bearing mice. Therefore, this work provided a versatile but effective method for neoantigen peptide and CpG ODN co-assembly vaccine platform for efficient colorectal cancer immunotherapy.