GSE264352 Enfortumab Vedotin Induces Immunogenic Cell Death and Shows Enhanced Preclinical Antitumor Activity When Combined With a PD-1 Inhibitor

Contributors : Devra J Olson ; Patrick Younan ; Bernard A Liu ; Gabriele Blahnik-Fagan ; John J Gosink ; Katie Snead ; Elena Tenn ; Kelly Hensley ; Disha Saheytya ; Albina Nestrerova ; Margo Zaval ; Anthony Cao ; Christine O'Day ; Ryan A Heiser ; Timothy S Lewis ; Shyra J Gardai ; Taisuke Nakazawa ; Masashi Shimazaki ; Christopher Carosina ; Sharsti SandallSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusEnfortumab vedotin is a Nectin-4-directed antibody –drug conjugate designed to deliver the microtubule-disrupting agent monomethyl auristatin E (MMAE) in tumor cells. Using preclinical models of urothelial cancer (UC), we expand the understanding of the multifaceted mechanism of action for enfortumab vedotin that includes direct cytotoxicity on Ne ctin-4–positive tumor cells, indirect bystander effect on neighboring Nectin-4–negative tumor cells, and MMAE-mediated induction of immunogenic cell death (ICD) and associated increase in activated immune cells in the tumor microenvironment. Importantly, vaccination with enfortumab vedotin-treat ed tumor cells drives antitumor immunity and provides protection against rechallenge in mice. MMAE-mediated ICD induction modulates the tumor microenvironment in a complementary manner to immune checkpoint inhibition. Accordingly, enfortumab vedotin plus PD-1 inhibitor shows enhanced antitumor activ ity in vivo. These preclinical results demonstrate the underlying mecha...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Mus musculus Source Type: research