Strategies for Dodging the Obstacles in CAR T Cell Therapy

• Main Authors: Pooria Safarzadeh Kozani, Pouya Safarzadeh Kozani, Fatemeh Rahbarizadeh, Shahryar Khoshtinat Nikkhoi
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-04-01
• Series: Frontiers in Oncology
• Subjects: chimeric antigen receptor; immunotherapy; tumor microenvironment; toxicities; adoptive cell therapy; solid tumors
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.627549/full

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Adverse events such as cytokine release syndrome (CRS), neurotoxicity, graft rejection, on-target off-tumor toxicities, and tumor relapse have tied the rescuing hands of CAR T cell therapies. Moreover, in the case of solid tumor treatment, CAR T cell therapies have not yielded encouraging results mainly due to challenges such as the formidable network of the tumor microenvironments (TME) that operates in a suppressive fashion resulting in CAR T cell dysfunction. In this review, we tend to shine a light on emerging strategies and solutions for addressing the mentioned barriers. These solutions might dramatically help shorten the gap between a successful clinical outcome and the hope for it.