CAR T Cell On-Target, Off-Tumor Toxicity in Solid Tumor Treatment: Generation and Management

Abstract

CAR-T cells involve incorporating T cells with a synthetic receptor to target tumor-specific molecules and this therapy enhances the patients’ own immune system to combat tumors. CAR-T cells are successful to elicit an enduring response to hematological malignancies but remains unsatisfactory during their application in solid tumors. Mostly, OTOT is a main safety concern during trials of CAR-T cells, which has led to destruction of healthy tissues and their normal functions, potentially threatening the patients’ life if damage were done on essential organs. OTOT arises from the CAR-T activation upon normal cells due to presence of tumor-like molecules on their surfaces, accompanied by potential cytokine release syndrome (CRS), which further lyses normal tissues. In this review, the structure and mechanisms of CAR-T cells will be described. More importantly, we will discuss the OTOT generation in CAR-T trials targeting solid tumors and available methods to mitigate this problem for advancing CAR-T application.