CAR-mediated target recognition limits TCR-mediated target recognition of TCR- and CAR-dual-receptor-edited T cells.

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả: J H Frederik Falkenburg, Renate S Hagedoorn, Mirjam H M Heemskerk, Miranda H Meeuwsen, Teuntje Poortvliet, Dennis F G Remst, Marijke F Toes, Tassilo L A Wachsmann, Anne K Wouters

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Molecular therapy : the journal of the American Society of Gene Therapy , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 734791

Antigen escape can compromise the efficacy of chimeric antigen receptor (CAR-) or T cell receptor (TCR-) engineered T cells. Targeting multiple antigens can effectively limit antigen escape, and combining CAR- with TCR-mediated targeting can significantly broaden the spectrum of targetable antigens. Here, we explored whether dual-antigen specificity can be installed on T cells using combined TCR- and CAR-engineering to prevent antigen escape of multiple myeloma (MM). We report the generation of CD8 T cells that were transduced to express a transgenic TCR, targeting a peptide derived from transcriptional coactivator BOB1 in the context of HLA-B*07:02, alongside a BCMA-targeting CAR. Those T cells, termed TRaCR T cells, efficiently recognized target cells that were resistant to either BOB1 TCR or BCMA CAR T cells, illustrating general dual-specificity. In the presence of both antigens however, target cell recognition was preferentially conferred via the CAR, compromising TCR-mediated target cell recognition. Importantly, this resulted in a survival advantage for tumor cells lacking expression of BCMA in an in vivo model of heterogenous MM. In conclusion, we demonstrate general dual-specificity of TRaCR T cells but advise caution when using TRaCR T cells as strategy to target heterogenous tumors.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 36225755 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH