T-cell engagers mediate deep cell depletion beyond autoimmunity.

Abstract

Deep B-cell and plasma cell depletion is rapidly reshaping the therapeutic landscape. Initially developed for hematologic malignancies, T cell-redirecting therapies (chimeric antigen receptor T cells and T-cell engagers) are now demonstrating profound efficacy in autoimmune diseases. The first successful application of a B-cell maturation antigen-targeting T-cell engager to achieve human leukocyte antigen desensitization in a highly sensitized kidney transplant candidate marks yet another critical milestone: This success signals a "spillover" of deep cell depletion into nonmalignant, nonautoimmune indications and paves the way for novel strategies in transplantation tolerance, severe allergic diseases, and beyond.