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Table 6 Combination strategies to enhance the efficacy of adoptive cell therapy

From: Combination strategies to maximize the benefits of cancer immunotherapy

Category Example Mechanisms
Combination with negative immune regulator blockade Immune checkpoint inhibitor Remove the suppression of CAR cell function through the checkpoint pathway
Knockout TGF-β signaling in CAR cells Enhance CAR cell function and alter TME
Combination with lymphodepletion Fludarabine and cyclophosphamide Suppress immune response and elimination of CAR cells
Deplete Treg and other competing immune cells
CAR T cell combination Two CAR cells targeting the same molecule Overcome immune elimination of the first CAR cells
Two CAR cells targeting the different molecules Maximize therapeutic effects and reduce antigen escape
Combination with immune modulators Exogenous immune modulators Stimulate CAR cells and other cytotoxic immune cells and reduce immunosuppressive cells
Fourth-generation CAR T cells Deliver immune regulators at cancer sites
Combination with TKI CAR T cells with ibrutinib Exert direct antitumor activity, downregulate PD1/PD-L1, tilt from Th2 to Th1, suppress MDSC, etc
Combination with oncolytic virotherapy Armed oncolytic adenovirus Exert direct lysis and killing of cancer cells, stimulate innate immune response, alter TME, cytokine to attract and stimulate CAR T cells