CAR T-cell therapy for B-cell lymphomas: outcomes and resistance mechanisms. Cancer Metastasis Rev 2024 Dec 01;44(1):12
Date
12/02/2024Pubmed ID
39617795DOI
10.1007/s10555-024-10228-0Scopus ID
2-s2.0-85211169496 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Chimeric antigen receptor (CAR) T cells are an exciting curative intent approach to the treatment of non-Hodgkin lymphomas (NHLs). Several products have received FDA approval for 2nd or 3rd line indications, and studies are underway for their use earlier in the disease course. These CAR T cells are ex vivo manufactured autologous cell products that specifically target tumor antigens to optimize tumor specificity and minimize off-tumor side effects-in NHLs, this is typically achieved by targeting B-cell antigens. Engagement of the CAR and corresponding antigen is designed to result in T-cell activation and subsequent tumor clearance. While curative for many NHL patients, too many patients fail to respond to or relapse following CAR T-cell treatment, and salvage options post CAR T-cell therapy are limited. Treatment failures occur because of myriad resistance mechanisms including CAR T-cell dysfunction, generalized immune dysregulation, and intrinsic tumor resistance. Focusing on patients with NHL, we review the clinical outcomes of CAR T-cell therapy and the major resistance mechanisms that lead to poor outcomes. We also review the many innovative and encouraging strategies that are being developed to improve CAR T-cell therapy for NHL.
Author List
Kearl TJ, Furqan F, Shah NNAuthors
Tyce J. Kearl PhD, MD Assistant Professor in the Medicine department at Medical College of WisconsinNirav N. Shah MD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsDrug Resistance, Neoplasm
Humans
Immunotherapy, Adoptive
Lymphoma, B-Cell
T-Lymphocytes
Treatment Outcome
