Oncolytic adenoviruses encoding bispecific T cell engagers or a novel trispecific T cell engager for dual-targeting of c-MET and EGFR
Year: 2025
Type: article
Abstract: , encouraging the design of the diabody-based trispecific TCE (Db-TriTE) scDb-cMET-scFv-EGFR. The Db-TriTE exhibited effective dual-targeting, i.e., the induction of cytotoxicity for single-positive cells of both targets and superior efficacy on double-positive cells. Therefore, a panel of oAds was produced to test different TCE (co-)expression strategies. Our results showed no or minor attenuation of viruses harboring the transgenes for one of the analyzed insertion strategies, expression of TCEs, and specific induction of both T cell activation and cytotoxicity in co-cultures of infected tumor cells with peripheral blood mononuclear cells (PBMCs). Importantly, we demonstrated dual-targeting by oAds encoding the two bispecific TCEs or the Db-TriTE with the latter featuring superior genomic stability and the overall highest efficacy. Taken together, we report novel bi- and trispecific TCEs and proof of principle for their application as dual-targeted viro-antibody therapy.
Source: Molecular Therapy Oncology
Authors: Martin A. Boos, Oliver Seifert, Stefanie Sawall, Jessica Genz, Annika Huber, Ilse Hofmann, Roland E. Kontermann, Guy Ungerechts, Dirk M. Nettelbeck
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
OpenAlex ID: W7110795754