Emerging vistas in CAR T-cell therapy: challenges and opportunities in solid tumors

Abstract

Introduction: Despite advances in modern evidence-based medicine, cancer remains a major cause of global disease-associated mortality. CAR T-cell therapy is a major histocompatibility complex (MHC)-independent immunotherapy involving adoptive cell transfer. Cancer immunotherapy witnessed a major breakthrough with the US FDA approval of the first chimeric antigen receptor (CAR) T-cell therapy Kymriah^TM (tisagenlecleucel) for relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) in August 2017 followed by approval of Yescarta® (axicabtagene ciloleucel) for R/R non-Hodgkin's lymphoma (NHL) in October 2017.

Areas covered: We review the potential of CAR T-cell therapy which, despite showing great promise in hematological malignancies, faces significant challenges in targeting solid tumors. We address these challenges and discuss proposed strategies to overcome them in solid tumors. We highlight the potential of CAR T-cell therapy as cancer precision medicine and briefly discuss the 'financial toxicity' of CAR T-cell therapy.

Expert opinion: Taken together, we discuss various strategies to circumvent the limitations of CAR T-cell therapy in solid tumors. Despite the rapid advances in CAR NK-cell therapies, there is immense scope for CAR T-cell therapy in solid tumors. We provide a synthetic review of CAR T-cell therapy that will drive future research and harness its full potential in cancer precision medicine for solid tumors.

Keywords: Adoptive cell transfer; CAR T-cell therapy; Kymriah; Yescarta; cancer; chimeric antigen receptor; immunotherapy; solid tumors.