CAR T-Cell Therapy in Hematological Malignancies: Mechanisms, Innovations, and Challenges
9 affiliations
- 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan
- 2College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates
- 3Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan
- 4Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan
- 5Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan
- 6Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan
- 7School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India
- 8School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, India
- 9North Wales Medical School, Bangor University, Brigantia Building, Penrallt Road, Bangor LL57 2AS, UK
Abstract
Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed or refractory hematological malignancies, producing deep and durable responses in B-cell acute lymphoblastic leukemia, aggressive B-cell non-Hodgkin lymphomas, and multiple myeloma. Nevertheless, antigen escape, limited in vivo persistence, T-cell exhaustion, and toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit broader application. This review synthesizes the mechanistic basis and clinical evidence for the currently approved CAR T-cell products and examines engineering strategies designed to overcome these barriers, including “armored” CAR T cells, multitargeted and logic-gated constructs, and modular or universal platforms intended to extend this approach beyond CD19-positive disease. Combination strategies with immune checkpoint inhibitors, radiotherapy, and other immunotherapies are discussed, together with emerging biomarkers of response and toxicity. Continued optimization of CAR design, toxicity management, and manufacturing scalability will be essential for CAR T-cell therapy to become a foundational pillar of precision oncology.
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BibTeX
@article{aljabali2026tcell,
title = {{CAR T-Cell Therapy in Hematological Malignancies: Mechanisms, Innovations, and Challenges}},
author = {Alaa A. A. Aljabali and Mohammad A. Obeid and Abdelrahim Alqudah and Yassmen Hamzat and Alaa Alqudah and Lorca Alzoubi and Omar Gammoh and Esam Qnais and Vijay Mishra and Yachana Mishra and Taher Hatahet and Mohamed El-Tanani},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203254},
url = {https://www.mdpi.com/2072-6694/18/20/3254},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CAR T-Cell Therapy in Hematological Malignancies: Mechanisms, Innovations, and Challenges
AU - Alaa A. A. Aljabali
AU - Mohammad A. Obeid
AU - Abdelrahim Alqudah
AU - Yassmen Hamzat
AU - Alaa Alqudah
AU - Lorca Alzoubi
AU - Omar Gammoh
AU - Esam Qnais
AU - Vijay Mishra
AU - Yachana Mishra
AU - Taher Hatahet
AU - Mohamed El-Tanani
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203254
UR - https://www.mdpi.com/2072-6694/18/20/3254
AB - Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of relapsed or refractory hematological malignancies, producing deep and durable responses in B-cell acute lymphoblastic leukemia, aggressive B-cell non-Hodgkin lymphomas, and multiple myeloma. Nevertheless, antigen escape, limited in vivo persistence, T-cell exhaustion, and toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit broader application. This review synthesizes the mechanistic basis and clinical evidence for the currently approved CAR T-cell products and examines engineering strategies designed to overcome these barriers, including “armored” CAR T cells, multitargeted and logic-gated constructs, and modular or universal platforms intended to extend this approach beyond CD19-positive disease. Combination strategies with immune checkpoint inhibitors, radiotherapy, and other immunotherapies are discussed, together with emerging biomarkers of response and toxicity. Continued optimization of CAR design, toxicity management, and manufacturing scalability will be essential for CAR T-cell therapy to become a foundational pillar of precision oncology.
SN - 2072-6694
ER -