ABSTRACT mRNA‐based tumor vaccines have shown great potential as a promising immunotherapeutic approach with encouraging preclinical and clinical results. However, how to enhance the antigen presentation efficiency of mRNA‐encoded tumor antigens and the intensity of vaccine‐induced CD8 + T cell response remains a great challenge. In this study, an antigen‐angiotensin II (ANG II) fusion mRNA nanovaccine that can enhance the immunogenicity of tumor antigens to promote CD8 + T cell immunity for effective tumor inhibition is developed. Furthermore, this mRNA nanovaccine is delivered by lipid nanoparticles (LNPs) composed of cationic lipid‐like material C1 and L‐phenylalanine‐based poly (ester amide) 8p4, which promotes the maturation of dendritic cells (DCs) and increases the type 1 conventional DC (cDC1) subpopulation, together enhancing the antigen presentation function of DCs for eliciting potent antigen‐specific CD8 + T cell response. Vaccination with the antigen‐ANG II mRNA nanovaccine expressing different tumor antigens effectively inhibited tumor growth on multiple mouse tumor models, which was greatly compromised in the cDC1‐deficient Batf3 −/− mice. Overall, this work provides an antigen‐ANG II fusion mRNA tumor nanovaccine platform with remarkable antitumor efficacy via triggering cDC1‐mediated CD8 + T cell response.
Xie et al. (Mon,) studied this question.