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

UMG1 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 BCL2(high) and CD20(low) cases. UMG1 membrane expression was also found in DLBCL bone marrow-infiltrating cells and established cell lines. Targeting UMG1 with a novel asymmetric UMG1/CD3 epsilon-bispecific T-cell engager (BTCE) induced redirected cytotoxicity against DLBCL cells and was synergistic with lenalidomide. We conclude that UMG1/CD3 epsilon-BTCE is a promising therapeutic for DLBCLs.

Automated summary

UMG1 is a unique epitope of CD43, expressed in thymocytes and a minority of peripheral blood T lymphocytes, and highly expressed in DLBCL. Targeting UMG1 with UMG1/CD3 epsilon-BTCE induces cytotoxicity against DLBCL cells and shows synergy with lenalidomide, suggesting its potential as a therapeutic for DLBCL.