Recent advances in mRNA-based cancer vaccines encoding immunostimulants and their delivery strategies

The high prevalence of drug resistance, relapse, and unfavorable response rate of conventional cancer therapies necessitate the development of more efficient treatment modalities. Immunotherapy represents a novel therapeutic approach to cancer treatment in which the immune system's potential is harnessed to recognize and eliminate tumor cells. mRNA cancer vaccines, as a burgeoning field of immunotherapy, have recently drawn particular attention, and among mRNAs encoding tumor-associated antigens, tumor-specific antigens, and immune stimulatory factors, the latter has been relatively less explored. These immunostimulatory mRNAs encode a range of proteins, including stimulatory ligands, receptors, enzymes, pro-inflammatory cytokines, and inhibitory binding proteins, which collectively augment the host immune system's ability against cancerous cells. In this review, we aimed to provide a comprehensive account of mRNA-based cancer vaccines encoding immune stimulants, encompassing their current status, mechanisms of action, delivery strategies employed, as well as recent advances in preclinical and clinical studies. The potential challenges, strategies and future perspectives have also been discussed.