In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 14, No. 634 ( 2022-03-02)
Abstract:
A major challenge with chimeric antigen receptor (CAR) T cell therapy is the inability of CAR T cells to distinguish tumors from healthy tissue. This is especially a challenge for solid tumors, where few tumor-specific antigens exist. To address this problem, Sandberg et al . developed modular T (Tmod) cells. This construct combines a CAR targeting carcinoembryonic antigen (CEA), a protein not only highly expressed on tumor cells but also expressed on healthy tissue, with a blocker module targeting human leukocyte antigen (HLA)–A*02. The HLA-A*02 blocker prevents CAR-mediated killing of all healthy cells expressing HLA-A*02. However, in tumor cells with HLA-A*02 loss of heterozygosity, the blocker is no longer activated, allowing the CEA-specific CAR to mediate tumor cell killing. The authors show that the CEA Tmod can selectively kill HLA-A*02 negative cells in vitro and in vivo, leaving HLA-A*02–expressing cells intact. These data suggest that two-receptor systems such as Tmod could be used to selectively and safely target antigens that are expressed on both tumor cells and normal tissues.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abm0306
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2022
detail.hit.zdb_id:
2518839-2
detail.hit.zdb_id:
2518854-9
Permalink