Engineering of a trispecific tumor-targeted immunotherapy incorporating 4-1BB co-stimulation and PD-L1 blockade
Stefan Warmuth, Tea Gunde, Daniel Snell, Matthias Brock, Christopher Weinert, Alexandre Simonin, Christian Hess, Julia Tietz, Maria H. Johansson, Fabio M. Spiga, Robin Heiz, Naomi Flückiger, Sandro Wagen, Julia Zeberer, Dania Diem, Dana Mahler, Belinda Wickihalder, Simone Muntwiler, Bithi Chatterjee, Benjamin Küttner, Bettina Bommer, Yasemin Yaman, Peter Lichtlen, David Urech
Abstract
that was largely independent of PD-L1 density. NM21-1480 exhibited high efficacy for co-activation of pre-stimulated T cells and dendritic cells. In xenograft models in syngeneic mice, NM21-1480 induced tumor regression and tumor infiltration of T cells without causing systemic T-cell activation. A GLP toxicology study revealed no evidence of liver toxicity at doses up to 140 mg/kg, and pharmacokinetic studies in non-human primates suggested a plasma half-life in humans of up to 2 weeks. NM21-1480 has the potential to overcome checkpoint resistance by co-activating tumor-infiltrating lymphocytes without liver toxicity.