Combination therapy: A feasibility strategy for CAR‑T cell therapy in the treatment of solid tumors (Review)

Abstract

Chimeric antigen receptor (CAR) T-cell therapies have been demonstrated to have durable and potentially curative therapeutic efficacies in patients with hematological malignancies. Currently, multiple clinical trials in CAR-T cell therapy have been evaluated for the treatment of patients with solid malignancies, but have had less marked therapeutic effects when the agents are used as monotherapies. When summarizing relevant studies, the present study found that combination therapy strategies for solid tumors based on CAR-T cell therapies might be more effective. This review will focus on various aspects of treating solid tumors with CAR-T cell therapy: i) The therapeutic efficacy of CAR-T cell monotherapy, ii) the feasibility of the CAR-T cell therapy in conjunction with chemotherapy, iii) the feasibility of CAR-T cell therapy with radiotherapy, iv) the feasibility of CAR-T cell therapy with chemoradiotherapy, and v) the feasibility of the combination of CAR-T cell therapy with other strategies.

CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?

“…While this review has focused on additional genetic modification to improve the effector function of CAR T cells, numerous studies are underway to combine CAR T cell therapy with other treatment modalities to improve outcomes by creating therapeutic synergies. 269,270 These include efforts, as already mentioned in this review, to combine CAR T cell therapy with cytokine administration, checkpoint blockade, oncolytic viruses, radiation, and/or vaccines. Examples for oncolytics/CAR T cell therapy combinations include the administration of oncolytic viruses encoding BiTEs, cytokines, and/or checkpoint inhibitors, [271][272][273] or oncolytic viruses that encode CAR targets.…”

Clinical CAR-T Cell and Oncolytic Virotherapy for Cancer Treatment

“…Additionally, chemotherapy has reduced immunosuppressive cells in the TME and improved tumor antigen expression, which has contributed to synergistic benefits between this conventional therapy and CAR-T cells. 117…”

Surmounting the obstacles that impede effective CAR T cell trafficking to solid tumors

“…Previously, the effect of ablative radiotherapy upon primary tumor and metastasis was reported to be strongly dependent on CD8 + T cell response 92 . Radiotherapy seems to induce an inflammatory milieu, which might favor increased vascular adhesion and chemotaxis‐driven migration 93,94 . In addition, irradiation of cancer cell lines led to increased expression of tumor‐associated antigens 95,96 .…”

“…92 Radiotherapy seems to induce an inflammatory milieu, which might favor increased vascular adhesion and chemotaxis-driven migration. 93,94 In addition, irradiation of cancer cell lines led to increased expression of tumor-associated antigens. 95,96 Therefore, an efficient CAR T cell migratory and infiltration capabilities might benefit from a combination to a classical radiotherapy to treat solid tumors.…”