Emerging Trends in Chimeric Antigen Receptor (CAR)-Based Cellular Immunotherapies

Dear Colleagues,

Adoptive cell therapy (ACT) is an advanced approach to cancer treatment in which a patient’s immune cells can be removed, engineered, expanded ex vivo, and transferred back into the patient to boost the anti-tumor immune response. The chimeric antigen receptor T (CAR-T) cell is a form of ACT that has revolutionized treatment for hematological malignancies. So far, the U.S. FDA has approved six CAR-T therapies, and more than 100 companies are currently involved in developing CAR-T-based cellular immunotherapies. However, the success of CAR-T therapy for the treatment of solid tumors remains limited due to (1) antigen heterogeneity in solid tumors, (2) T-cell exhaustion, (3) inability to infiltrate solid tumors, or (4) immunosuppressive tumor microenvironment (TME). In addition, strategies to overcome adverse events (AEs) associated with current CAR-T treatments, such as cytokine release syndrome (CRS), CAR T-cell-related encephalopathy syndrome (CRES), and immune-effector-cell-associated neurotoxicity syndrome (ICANS), are also an active area of investigation.

Hence, there is enormous room for improvement, and efforts are currently underway to design the next generation of CAR-based cellular immunotherapies in various immune-cell types, such as in macrophages (CAR-M or CAR-P), natural killer (NK) cells (CAR-NK), in addition to improving the efficacy of CAR-T cells for solid tumors. The first-in-human CAR-M clinical trial is already in progress for breast cancer treatment. The approaches for streamlining the CAR-M platform for treatment include the generation of allogeneic iPSC-derived CAR-M, CAR monocytes, and optimizing combination therapies.

We invite the submission of original articles and reviews discussing the emerging trends in CAR-based immunotherapies for solid and hematological malignancies, chimeric engulfment receptor (CER) technology, biomarkers for CAR-based therapies, dendritic cell (DC) and regulatory (Treg) T-cell-based immunotherapies, multiplexing CAR, and CAR-based combination therapies. In addition, novel modalities for in vivo CAR therapies (e.g., mRNA-lipid nanoparticles) or pre-clinical investigations are also welcome.

Dr. Abhinava Mishra
Dr. Sandeep Kumar
Guest Editors

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