Title
Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response
Date Issued
01 December 2019
Access level
open access
Resource Type
journal article
Author(s)
Baeuerle P.A.
Ding J.
Patel E.
Thorausch N.
Horton H.
Gierut J.
Scarfo I.
Choudhary R.
Kiner O.
Krishnamurthy J.
Le B.
Morath A.
Quinn J.
Tavares P.
Wei Q.
Weiler S.
Maus M.V.
Getts D.
Schamel W.W.
Hofmeister R.
TCR² Therapeutics
Publisher(s)
Nature Publishing Group
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.
Volume
10
Issue
1
Language
English
OCDE Knowledge area
Inmunología Oncología
Scopus EID
2-s2.0-85065335775
PubMed ID
Source
Nature Communications
ISSN of the container
20411723
Sponsor(s)
We thank Kerstin Fehrenbach for technical assistance. This work was in part supported by the Excellence Strategy of the German Federal and State Governments (CIBSS - EXC 2189 and BIOSS - EXC294, WWS) and GSC-4 (Spemann Graduate School, AM).
Sources of information: Directorio de Producción Científica Scopus