UMG1/CD3ε-bispecific T-cell engager redirects T-cell cytotoxicity against diffuse large B-cell lymphoma
- Autori: Caracciolo, Daniele; Polerà , Nicoletta; Belmonte, Beatrice; Conforti, Francesco; Signorelli, Stefania; Gulino, Alessandro; Staropoli, Nicoletta; Tuccillo, Franca Maria; Bonelli, Patrizia; Juli, Giada; Grillone, Katia; Ascrizzi, Serena; Cirillo, Maria; Migale, Leonardo; Ballerini, Andrea; Pelizon, Cristina; Di Martino, Maria Teresa; Tagliaferri, Pierosandro; Riillo, Caterina; Tassone, Pierfrancesco
- Anno di pubblicazione: 2023
- Tipologia: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/619456
Abstract
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.