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Nov 19, 2019

Seminar - A novel approach to engineer T cells for cancer therapy (Speaker: Professor Dr. Patrick A. Baeuerle)

Professor Dr. Patrick A. Baeuerle
TCR2 Therapeutics Inc., Cambridge, USA
Honorary Professor of Immunology
Munich University's Medical School, Germany

Date: Tuesday, 19-November-2019
Time: 4:00 p.m.
Venue: Seminar Room 6, LG1/F, Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Pokfulam, Hong Kong​

Autologous T cells engineered to express either a chimeric antigen receptor (CAR-T cells) or pre-defined TCR alpha and beta subunits (TCR-T cells) have shown stunning therapeutic activity in the treatment of hematological and solid tumors, respectively. CAR-T cells recognize cell surface antigens on cancer cells and are therefore independent of HLA context. CARs however lack most subunits of the T cell receptor (TCR) that govern many regulatory aspects of T cell activation resulting in aberrant signaling. TCR-T cells, while engaging the entire TCR complex, are restricted by HLA type and often require engineering of alpha and beta subunits for high-affinity recognition of peptide/HLA complexes. Professor Baeuerle‘s team have designed a novel approach to engineer T cells that essentially “marries” CAR-T with TCR-T cell technology: By fusing antigen-binding domains directly to CD3 gamma, delta, or epsilon subunits or to TCR alpha and TCR beta chains of the TCR, they can reprogram an entire TCR complex to recognize a cell surface antigen and accordingly redirect T cells for lysis of target cells. The recombinant fusion of an antigen-binding domain to TCR subunits is referred to as “T cell receptor fusion construct”, or TRuC. TRuCs are shown to be incorporated into the TCR complex and elicit all hallmarks of T cell activation in response to recognition of cell surface antigens. Despite the absence of additional costimulatory domains, as otherwise used by CARs, TRuC-T cells show on several accounts superior performance vis-à-vis CAR-T cells that are made using the same antigen-binding domain. A novel therapy based on TRuC-T cells targeting mesothelin (TC-210) for treatment of solid tumors has commenced clinical trials.