Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors

Abstract

Checkpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response. This can be further amplified by the addition of CPB agents, which serve to counteract the immune inhibitory environment undermining optimal CAR T cell efficacy. Herein, we review preclinical and clinical combination therapy with CAR T cells and CPB agents, with a focus on solid tumor malignancies.

CAR-T Cell Therapy in Cancer: Tribulations and Road Ahead

“…In addition, the overexpression of HPSE in CAR-T cells can effectively degrade extracellular matrix and effectively infiltrate tumor tissue. Another strategy can be implemented to increase the infiltration of T cells into tumor, to achieve the goal of increasing cells in the tumor that induce local inflammatory conditions using conventional cancer treatment methods such as radiotherapy and chemotherapy [62].…”

“…Currently, clinical trials specifically blocking PD-1 and using CAR-T cell therapy are underway. Tumor cells overexpressing PD-L1 and PD-L2 reduce the tumor suppression mediated by CAR-T cells, thereby increasing tumor cell survival [62]. Targeting immunosuppressive pathways in the TME can cause a sustained antitumor response in advanced-stage patients, with an unusual effect on cancer progression.…”

The ICOSL Expression Predicts Better Prognosis for Nasopharyngeal Carcinoma via Enhancing Oncoimmunity

“…Immunocheckpoint immunotherapy has brought a deep revolution for cancer treatment; therefore, investigating more immunocheckpoint proteins or pathways is a hot point [8]. ICOSL-ICOS axis is one of the important costimulatory axes in the immune system [9].…”

“…Knocking down ICOSL did not change the proliferation, migration, and invasion ability of NPC cells in vitro. (a) mRNA and protein levels from four NPC cell lines; (b) qRT-PCR and western blot prove that ICOSL siRNA strongly reduces the ICOSL production in NPC cell in both mRNA and protein levels; (c) MTT assay shows that reduced ICOSL does not change the proliferation ability of NPC cells; (d) reduced ICOSL did influence the migration capability of NPC cells; (e) reduced ICOSL did influence the invasion capability of NPC cells 8. BioMed Research International…”

Interleukin-7 loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma

“…CAR-T cells with self-secreting cytokines, or taking use of auxiliary therapy to reverse the immunosuppressive tumor microenvironment [5,6].…”