Abstract:
:T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T cells are shown to engage the signaling capacity of the entire TCR complex in an HLA-independent manner.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Baeuerle PA,Ding J,Patel E,Thorausch N,Horton H,Gierut J,Scarfo I,Choudhary R,Kiner O,Krishnamurthy J,Le B,Morath A,Baldeviano GC,Quinn J,Tavares P,Wei Q,Weiler S,Maus MV,Getts D,Schamel WW,Hofmeister Rdoi
10.1038/s41467-019-10097-0subject
Has Abstractpub_date
2019-05-07 00:00:00pages
2087issue
1issn
2041-1723pii
10.1038/s41467-019-10097-0journal_volume
10pub_type
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