2019台灣生技月 Bio Taiwan 生物科技大展

2019 台灣生技月 南港展覽館

講師

Robert Hofmeister

Session 7 – Cell & Gene Therapies
Date: 26 July (Friday)  9:00 – 12:00
Venue: 3F, Bldg. A, CTBC Financial Park, Ballroom A
 


 

Robert Hofmeister

Chief Scientific Officer
TCR2 Therapeutics, Inc.

 
Dr. Hofmeister joined TCR² in 2015 as the Senior Vice President of Research and Development. He brings two decades of scientific leadership and a successful track record of drug discovery and early development. Previously, Dr. Hofmeister was the Vice President of Immuno-Oncology at EMD Serono where he was involved in the development of now approved Bavencio® (avelumab) and building the company’s immuno-oncology platform. He started his biotech career at Micromet AG, now Amgen Research Munich, where he helped shape the development of Blincyto®, the first FDA-approved bispecific antibody for the treatment of relapsed/refractory ALL. Dr. Hofmeister received his PhD from the University of Regensburg in Germany, where he studied the signaling of the cytokine interleukin-1. He continued to work in the cytokine field as a postdoctoral fellow at the National Cancer Institute.

Session Speech Title & Synopsis:
TRuC™-T Cells: Redefining T Cell Therapy for Cancer
 
T cells have evolved as our body’s most potent killers against tumor cells. The T cell receptor (TCR) is a protein complex on the cell surface comprising six different subunits, each of them playing a critical role in defining a potent and well controlled anti-tumor response. Due to its central role for T cell activation, a number of engineering approaches have focused on the TCR. Chimeric antigen receptors (CARs) reduce the complexity of the natural TCR to only one TCR subunit in combination with co-stimulatory domains. CAR-T cells show impressive responses in hematological tumors, but high cytokine release and underwhelming performance in solid tumors limit their applicability. In contrast, T cell therapies utilizing the entire TCR have seen greater success to date in treating solid tumors compared with CAR-T cells. Therefore, it is likely that T cells require the more comprehensive signaling of the complete TCR to be active against solid tumors. Here, we report that fusion of an antibody-based binding domain to TCR subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens without the requirement for human leukocyte antigen matching. Unlike CARs, T cell receptor fusion construct (TRuC™) variants become a functional component of the natural TCR complex and trigger a potent anti-tumor response without using an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor efficacy in liquid and solid tumor models, but at significant lower cytokine release potentially translating into a better safety profile. Our preclinical results show that cell activation through the complete TCR allows TRuC-T cells to traffic faster to tumors and show a favorable metabolic profile and long persistence required to prevent relapse. We recently initiated clinical trials for our lead TRuC-T cell program TC-210 and have a broad portfolio of other treatments moving toward the clinic.