Fig. 3
From: mRNA in cancer immunotherapy: beyond a source of antigen
The in vivo application of mRNA to modulate the tumor microenvironment. (1) Use of mRNA for induction of cell death in diseased cells e.g. mRNA encoding MLKL enforce cells to die in an immunogenic way [80] (2) Use of mRNA to modulate tumor-associated dendritic cells (TADC) e.g. mRNA encoding for CD40L, CD70 and caTLR4 (TriMix) can be combined to stimulate immature TADC to mature TADC [81,82,83,84]. (3) Use of mRNA to modulate suppressive cell types e.g. mRNA encoding IKKβ is used to genetic reprogram tumor-associated macrophages [85]. (4) The use of mRNA to modulate the cytokine milieu e.g. mRNA encoding IFN-β fused to the ectodomain of the TGF-β receptor II (Fβ2) [86]. (5) Use of mRNA for generation of cancer-specific T cells. mRNA can be used to genetic engineer T cells to express cancer-specific T cell receptors or chimeric antigen receptor. Abbreviations: MLKL: Mixed lineage kinase domain like pseudokinase; CD40L: Cluster of differentiation 40 ligand; CD70 Cluster of differentiation 70; caTLR4: constitutive active toll like receptor 4; M2: macrophage type 2 phenotype; M1: macrophage type 1 phenotype; IKKβ: Inhibitor of nuclear factor kappa-β kinase; MDSC: Myeloid-derived suppressor cell; CAF: Cancer-associated fibroblast; Fβ2: IFN-β fused to the ectodomain of the TGF-β receptor II; TCR: T cell receptor; CAR: chimeric antigen receptor