A combination of TLR9 and STING agonists induces potent neopeptide-specific T cell immunity and improves ICB efficacy in tumor models
The Journal of Immunology(2023)
摘要
Abstract Immunotherapies such as immune checkpoint blockade (ICB) therapies have been developed in the last years as a promising strategy for the treatment of cancer, however there remains a need to improve their efficacy. The most critical factor that affects the efficacy of ICB therapies, is the frequency of tumor mutations, the associated neoantigens generated and the T-cell response against them. Therefore, it is expected that neoantigen vaccinations would improve ICB therapy efficacy by boosting the neoantigen-specific T cell response. The aim of this study is to develop an effective vaccine using a combination of TLR9 and STING agonists together with synthetic long peptides to induce a potent neoantigen-specific cytotoxic CD8 +T cell response. We first analyzed the efficacy of the vaccine formulation containing 20-mer OVA peptide and found that mice immunized with OVA peptide together with the adjuvant combination induced potent antigen-specific T cell responses and are capable of controlling tumor growth and improving survival in B16-F10-OVA tumor bearing mice. Moreover, we found that the vaccine together with OVA peptide is able to synergize with anti-PD-1 treatment in controlling tumor growth. Finally, we examined the immunogenicity of the vaccine formulation with neopeptides identified from two different tumor models. The vaccine formulation induced potent neoantigen-specific T cell responses in vivo. Our findings demonstrate that the vaccine formulation using the combination of TLR9 and STING agonists induces potent T cell immunity against synthetic long peptides and can serve as a promising immunogenic neoantigen vaccine platform. Supported by the Department of Immunology of the Erasmus MC the Dutch Cancer Society (KWF grant 12837) and in part by a grant from International Joint Usage/Research Center, the Institute of Medical Science, the University of Tokyo, and Japan Agency for Medical Research and Development (AMED).
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关键词
tlr9,sting agonists,immunity,icb efficacy,neopeptide-specific
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