Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.

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.
Authors	Patrick A Baeuerle, Jian Ding, Ekta Patel, Niko Thorausch, Holly Horton, Jessica Gierut, Irene Scarfo, Rashmi Choudhary, Olga Kiner, Janani Krishnamurthy, Bonnie Le, Anna Morath, G Christian Baldeviano, Justin Quinn, Patrick Tavares, Qi Wei, Solly Weiler, Marcela V Maus, Daniel Getts, Wolfgang W Schamel, Robert Hofmeister
Journal	Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 2087 (05 07 2019) ISSN: 2041-1723 [Electronic] England
PMID	31064990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, CD19 Antigens, Neoplasm Receptors, Antigen, T-Cell Receptors, Artificial Recombinant Fusion Proteins Single-Chain Antibodies
Topics	Animals Antigens, CD19 (immunology) Antigens, Neoplasm (immunology) Cell Line, Tumor Female Humans Immunotherapy, Adoptive (methods) Mice Mice, Inbred NOD Neoplasms (immunology, therapy) Primary Cell Culture Protein Domains Receptors, Antigen, T-Cell (genetics, immunology) Receptors, Artificial (genetics, immunology) Recombinant Fusion Proteins (genetics, immunology) Single-Chain Antibodies (genetics, immunology) T-Lymphocytes (immunology) Treatment Outcome Xenograft Model Antitumor Assays

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