UMG1/CD3ε‐bispecific T‐cell engager redirects T‐cell cytotoxicity against diffuse large B‐cell lymphoma

Abstract

SummaryUMG1 is a unique epitope of CD43, not expressed by normal cells and tissues of haematopoietic and non‐haematopoietic origin, except thymocytes and a minority (<5%) of peripheral blood T lymphocytes. By immunohistochemistry analysis of tissue microarray and pathology slides, we found high UMG1 expression in 20%–24% of diffuse large B‐cell lymphomas (DLBCLs), including highly aggressive BCL2high and CD20low cases. UMG1 membrane expression was also found in DLBCL bone marrow‐infiltrating cells and established cell lines. Targeting UMG1 with a novel asymmetric UMG1/CD3ε‐bispecific T‐cell engager (BTCE) induced redirected cytotoxicity against DLBCL cells and was synergistic with lenalidomide. We conclude that UMG1/CD3ε‐BTCE is a promising therapeutic for DLBCLs.