TY - JOUR
T1 - ReCARving the future
T2 - bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights
AU - Ali, Alaa
AU - DiPersio, John F.
N1 - Publisher Copyright:
Copyright © 2024 Ali and DiPersio.
PY - 2024
Y1 - 2024
N2 - Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and the integration of CAR T cells with other therapeutic modalities. This comprehensive analysis underscores the synergistic potential of these strategies to enhance the safety, efficacy, and accessibility of CAR T-cell therapies, providing a forward-looking perspective on their evolutionary trajectory in cancer treatment.
AB - Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and the integration of CAR T cells with other therapeutic modalities. This comprehensive analysis underscores the synergistic potential of these strategies to enhance the safety, efficacy, and accessibility of CAR T-cell therapies, providing a forward-looking perspective on their evolutionary trajectory in cancer treatment.
KW - allogeneic CAR T cells
KW - CAR T-cell therapy
KW - gene editing
KW - immunosuppressive microenvironment
KW - immunotherapy
KW - synthetic biology
UR - http://www.scopus.com/inward/record.url?scp=85204512302&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1432799
DO - 10.3389/fimmu.2024.1432799
M3 - Review article
C2 - 39301026
AN - SCOPUS:85204512302
SN - 1664-3224
VL - 15
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1432799
ER -