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 |