Journal Article

From bench to bedside: the history and progress of CAR T cell therapy

Mitra, Aroshi, Ganguly, Siddhartha, Barua, Amrita, Feng, Qin, He, Bin, Huang, Luping

2023

Overview

Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by the Food and Drug Administration in 2017 for the treatment of pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia. As of April 2023, six CAR T cell therapies have been approved, demonstrating unprecedented efficacy in patients with B-cell malignancies and multiple myeloma. However, adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity pose significant challenges to CAR T cell therapy. The severity of these adverse events correlates with the pretreatment tumor burden, where a higher tumor burden results in more severe consequences. This observation is supported by the application of CD19-targeted CAR T cell therapy in autoimmune diseases including systemic lupus erythematosus and antisynthetase syndrome. These results indicate that initiating CAR T cell therapy early at low tumor burden or using debulking strategy prior to CAR T cell infusion may reduce the severity of adverse events. In addition, CAR T cell therapy is expensive and has limited effectiveness against solid tumors. In this article, we review the critical steps that led to this groundbreaking therapy and explore ongoing efforts to overcome these challenges. With the promise of more effective and safer CAR T cell therapies in development, we are optimistic that a broader range of cancer patients will benefit from this revolutionary therapy in the foreseeable future.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Acute lymphoblastic leukemia / Adverse events / Antibodies / Antigens / Autoimmune diseases / Bladder cancer / cancer immunotherapy / Cancer therapies / CD19 antigen / Cell therapy / Chemotherapy / Child / chimeric antigen receptor (CAR T) / Chimeric antigen receptors / Clinical trials / cytokine release syndrome / Cytokines / FDA approval / Humans / Immune checkpoint inhibitors / Immune system / Immunology / Immunotherapy / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Kidney cancer / Leukemia / Lung cancer / Lymphatic leukemia / Lymphocytes / Lymphocytes B / Lymphocytes T / Malignancy / Medical research / Melanoma / Metastasis / Multiple myeloma / Multiple Myeloma - etiology / Neurotoxicity / Neurotoxicity Syndromes - etiology / Patients / Pediatrics / Solid tumors / Systemic lupus erythematosus / T cell receptors / TCR - T cell receptor / Toxins / tumor burden / Tumors / United States / Vaccines / Young Adult