Challenges and optimal strategies of CAR T therapy for hematological malignancies

• Published in: Chinese medical journal Vol. 136; no. 3; pp. 269 - 279
• Main Authors: Zhang, Yajing, Xu, Yang, Dang, Xiuyong, Zhu, Zeyu, Qian, Wenbin, Liang, Aibin, Han, Weidong
• Format: Journal Article
• Language: English
• Published: China Lippincott Williams & Wilkins Ovid Technologies 05.02.2023; Lippincott Williams & Wilkins; Wolters Kluwer
• Subjects: Antigens; Blood cancer; Clinical trials; FDA approval; Graft versus host disease; Hematologic Neoplasms - therapy; Hematology; Humans; Immunotherapy, Adoptive; Leukemia; Lymphocytes; Lymphoma; Neurotoxicity; Receptors, Chimeric Antigen - therapeutic use; Remission (Medicine); Review; Stem cells; T cell receptors; Treatment Outcome; United States > US
• ISSN: 2542-5641; 0366-6999; 2542-5641
• DOI: 10.1097/CM9.0000000000002476

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.