John Desjarlais on T-cell engagers
From Antibodies! Ep. 2: Fc Engineering & Bispecifics with John Desjarlais · · The Antibody Society
“I think the biggest challenge, I don't really think it's so much about the immunoenvironment and whether or not there's enough T cells because you see drugs like tarlatuximab working in cancer types like small cell lung cancer that at least by RNA expression levels don't have a tremendous number of T cells compared to other histologies, the targets that seem to be working, particularly for T cell engagers, just happen to be highly selective targets, meaning they're selectively overexpressed in one or more tumor types, for the most part one tumor type relative to all of the other normal tissues, and then coupled on top of that is having the right kind of selectivity engineering to take advantage of that selective overexpression so that you can more effectively engage the tumor cells versus the normal cells.”
On , John Desjarlais, Executive Vice President of Research & Chief Scientific Officer at XENCOR INC, spoke about T-cell engagers during Antibodies! Ep. 2: Fc Engineering & Bispecifics with John Desjarlais on The Antibody Society.
About John Desjarlais
John Desjarlais, Executive Vice President of Research and Chief Scientific Officer at Xencor, appeared on the Antibodies! podcast recorded at the Antibody Engineering & Therapeutics conference in San Diego. During the conversation, Desjarlais discussed the application of T-cell engager bispecific antibodies in autoimmune disease, citing a paper by Georg Schett on CD19 CAR-T therapy for autoimmune conditions. He described a "gold rush" in deploying T-cell engager bispecific antibodies targeting B-cell antigens such as CD20, CD19, and BCMA, based on the hypothesis that B cells contribute to the pathogenesis of autoimmune diseases. Desjarlais noted that the field is working to determine the optimal depth and durability of B-cell depletion to achieve an "immune reset" while allowing the immune system to recover. Desjarlais also addressed challenges in using T-cell engagers for solid tumors, stating that the biggest challenge is not the immunoenvironment or T-cell presence, but rather the identification of highly selective targets that are overexpressed on tumor cells. He suggested that tri-specific antibodies targeting two tumor antigens could improve selectivity by requiring T cells to kill only when both targets are present, though he acknowledged technical challenges in developing such molecules with good developability and half-life.