Fig. 3
From: Adoptive neoantigen-reactive T cell therapy: improvement strategies and current clinical researches
Feasible strategies for the improvement of T cell antitumor function. A Engineer T cell signals. Signal 1: edit TCR genes or make TCR and CD8 αβ co-expression. Signal 2: join CD28 to CD3ζ combined with 4-1BB or OX40 to enhance activation signals, construct the chimeric switch receptor (e. g., CD28 linked to PD-1,CTLA-4 and TIGHT) to reverse inhibitory signals. Signal 3: modify cytokine receptors (e. g., IL-2 orthogonal receptor) and increase the expression of autologous or heterologous cytokines or chemokines. B Produce multiple-function T cells: optimize CARs, secrete cytokines and enzymes, release extracellular vesicles containing RNAs, express multiple chemokine receptors, and modify immunosuppressive signal receptors. C Universal strategies to restore and increase the expression of MHC (inducing IFNγ production, using epigenetic silence or autophagy inhibitors (a)) and MICA/B (anti-MICA/B antibody (b))