“…For example, co-delivery of stimulatory cytokines, such as GM-CSF, IL-12, and IL-15, with mRNA encoding tumor antigen in dendritic cell vaccines promotes remodeling of the TME, enhances cytotoxic T cell responses, and controls tumor growth in preclinical models (128)(129)(130)(131). Further, in situ vaccination with a cocktail of naked mRNAs encoding IL-12, GM-CSF, IL-15, and IFN-α4 promotes tumor infiltration of polyfunctional Th1-like CD4 + cells, cytotoxic CD8 + T cells, and pro-immune monocytic cell types while decreasing Tregs, leading to survival benefits in murine models of cancer including metastatic melanoma (132). Similarly, in melanoma patients, coexpression of immunostimulatory molecules, such as CD40L, CD70, and constitutively active TLR4 (TriMix, eTheRNA Immunotherapies), along with the tumor antigen mRNA potentiates APC maturation and cognate T cell activation (133,134).…”