John Desjarlais on B-cell depletion
From Antibodies! Ep. 2: Fc Engineering & Bispecifics with John Desjarlais · · The Antibody Society
“I think the real evolution that we're going to look for in that field is figuring out how much depth of B cell depletion do you want. It's generally understood that the deeper the better in terms of patient responses, but maybe more importantly, after the depth is what's the durability of that depletion. And so, can you find a sweet spot where you've got enough depth and durability of that B cell depletion to do this immune reset, but also allow the immune system to recover and be able to react against, you know, infectious pathogens.”
On , John Desjarlais, Executive Vice President of Research & Chief Scientific Officer at XENCOR INC, spoke about B-cell depletion 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.