Challenges and solutions to superior chimeric antigen receptor-T design and deployment for B-cell lymphomas
Student AuthorsJenny Gao
UMass Chan AffiliationsMedicine
Morningside Graduate School of Biomedical Sciences
RNA Therapeutics Institute
Document TypeJournal Article
MetadataShow full item record
AbstractChimeric antigen receptor-T (CAR-T) therapies represent a major breakthrough in cancer medicine, given the ex vivo-based technology that harnesses the power of one's own immune system. These therapeutics have demonstrated remarkable success for relapsed/refractory B-cell lymphomas. Although more than a decade has passed since the initial introduction of CAR-T therapeutics for patients with leukaemia and lymphoma, there is still significant debate as to where CAR-T therapeutics fit into the management paradigm, as consensus guidelines are limited. Competing interventions deployed in subsequent lines of therapy for aggressive lymphoma include novel targeted agents, bispecific antibodies, and time-honoured stem cell transplant. In this focused review, we discuss the major obstacles to advancing the therapeutic reach for CAR-T products in early lines of therapy. Such barriers include antigen escape, "cold" tumour microenvironments, host inflammation and CAR-T cell exhaustion. We highlight solutions including point-of-care CAR-T manufacturing and early T lymphopheresis. We review the evidence basis for early CAR-T deployment for B-cell lymphomas in light of the recent Food and Drug Administration (FDA) approval of three first-in-class anti-CD3/CD20 bispecific antibodies-mosunetuzumab, epcoritamab and glofitamab. We propose practical recommendations for 2024.
SourceGao J, Dahiya S, Patel SA. Challenges and solutions to superior chimeric antigen receptor-T design and deployment for B-cell lymphomas. Br J Haematol. 2023 Oct;203(2):161-168. doi: 10.1111/bjh.19001. Epub 2023 Jul 24. PMID: 37488074.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52689
Funding and AcknowledgementsUMass Center for Clinical and Translational Science. Grant Number: UL1TR001453
Rights© 2023 British Society for Haematology and John Wiley & Sons Ltd.