In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer

Somatic mutation-derived neoantigens are associated with patient survival in breast and ovarian cancer. These neoantigens are targets for cancer, as shown by the implementation of neoepitope peptides as can-cer vaccines. The success of cost-effective multi-epitope mRNA vaccines against SARS-Cov-2 in the pan-demic established a model for reverse vaccinology. In this study, we aimed to develop an in silico pipeline designing an mRNA vaccine of the CA-125 neoantigen against breast and ovarian cancer, respectively. Using immuno-bioinformatics tools, we predicted cytotoxic CD8' T cell epitopes based on somatic mutation-driven neoantigens of CA-125 in breast or ovarian cancer, constructed a self-adjuvant mRNA vaccine with CD40L and MHC-I-targeting domain to enhance cross-presentation of neoepitopes by den-dritic cells. With an in silico ImmSim algorithm, we estimated the immune responses post-immunization, showing IFN-c and CD8' T cell response. The strategy described in this study may be scaled up and imple-mented to design precision multi-epitope mRNA vaccines by targeting multiple neoantigens.(c) 2023 Elsevier Ltd. All rights reserved.