Advances in molecular targeted drugs in combination with CAR-T cell therapy for hematologic malignancies

Abstract

Molecular targeted drugs and chimeric antigen receptor (CAR) T cell therapy represent specific biological treatments that have significantly improved the efficacy of treating hematologic malignancies. However, they face challenges such as drug resistance and recurrence after treatment. Combining molecular targeted drugs and CAR-T cells could regulate immunity, improve tumor microenvironment (TME), promote cell apoptosis, and enhance sensitivity to tumor cell killing. This approach might provide a dual coordinated attack on cancer cells, effectively eliminating minimal residual disease and overcoming therapy resistance. Moreover, molecular targeted drugs can directly or indirectly enhance the anti-tumor effect of CAR-T cells by inducing tumor target antigen expression, reversing CAR-T cell exhaustion, and reducing CAR-T cell associated toxic side effects. Therefore, combining molecular targeted drugs with CAR-T cells is a promising and novel tactic for treating hematologic malignancies. In this review article, we focus on analyzing the mechanism of therapy resistance and its reversal of CAR-T cell therapy resistance, as well as the synergistic mechanism, safety, and future challenges in CAR-T cell therapy in combination with molecular targeted drugs. We aim to explore the benefits of this combination therapy for patients with hematologic malignancies and provide a rationale for subsequent clinical studies.

Keywords: CAR-T cell; Immune regulation; Molecular targeted drug; Resistance mechanism; Tumor microenvironment.