Abstract
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.
Highlights
Chimeric antigen receptor (CAR) T cells are genetically engineered T cells that possess the ability to recognize and target tumor cells with significant discrimination from healthy tissues
Researchers have indicated that myeloid-specific ablation of tyrosine hydroxylase using metyrosine can protect mouse models of lymphoma with stimulated macrophages from lethal complications of cytokine release syndrome (CRS) after CD19-based CAR T cell therapy [45]
Other studies have presented similar promising results demonstrating that CAR T cells generated using Vd2 T cells can migrate towards tumor cells and perform antigen cross-presentation [91]. These findings propose that gd CAR T cells can enter the tumor site and eliminate tumor cells alongside uptaking the target antigens which lead to stimulatory antigen presentation to tumor-infiltrating lymphocytes (TILs) with ab T cell receptor (TCR) [91]
Summary
Pooria Safarzadeh Kozani 1†, Pouya Safarzadeh Kozani 2,3†, Fatemeh Rahbarizadeh 1,4* and Shahryar Khoshtinat Nikkhoi 5. 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 Bcell acute lymphoblastic leukemia (B-ALL) and lymphoma. CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. 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.
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