296P Integrative discovery and preclinical validation establish RANKL, TIGIT, and CD47 triple blockade as a potent strategy for cervical cancer

Methods: This study employed a proprietary prediction process to identify MHC class I and II-restricted neoantigens and investigated their immunogenicity and antitumour efficacy using an mRNA-based cancer vaccine platform in a murine model of colorectal cancer (CRC).Additionally, we have explored combination therapies, such as immune checkpoint inhibitors (ICIs) and mRNA-based cytokine therapies, to enhance antigen-specific immune responses and anti-tumour efficacy.Results: Co-administration of our MHC-I and MHC-II-restricted neoantigens increased MHC-I-restricted antigen-specific CD8 + T cell immune responses and exhibited strong anti-tumour efficacy, significantly inducing cell-mediated immune responses.Notably, early-stage vaccination produced a robust anti-tumour effect.Furthermore, the mRNA vaccine prevented CRC recurrence and sustained neoantigen-specific immune responses with an increase in memory T cells.Combining the mRNA vaccine with immune checkpoint inhibitors (anti-mouse PD-1 and anti-Tim-3 antibodies) synergistically inhibited tumour growth.In addition, combination therapy with mRNA vaccine and mRNA-based cytokines, such as mGM-CSF, IL-12, and IL-15, demonstrated synergistic enhancement of antigen-specific immune responses and antitumour effects. Conclusions:These findings highlight the therapeutic potential of PCVs in CRC treatment and underscore the importance of early vaccination to enhance antitumour efficacy.Furthermore, the combination of PCVs with immunotherapies such as immune checkpoint inhibitors (ICI) and cytokines to enhance antigen-specific T cell responses suggests a promising approach in cancer immunotherapy.Legal entity responsible for the study: The authors.