Anti-tumor activity of an RNA-encoded antibody combining T-cell engagement and checkpoint inhibition
Thursday, July 17, 2025
6:08 PM - 6:19 PM EDT
Location: 119 B
Introduction: T cell-engaging (TCE) antibodies recruit cytotoxic T cells to tumors, providing a potent strategy for cancer therapy. Despite their success, most formats suffer from short circulation half-lives and manufacturing challenges (1). These limitations can be overcome by nanocarrier (NC)-mediated delivery of mRNA-encoded TCEs (2). Here, we investigated the in situ production and efficacy of two TCE trimerbodies, the anti-EGFR x anti-CD3 bispecific ATTACK (3) and, as a further development, the anti-PD-L1 x anti-EGFR x anti-CD3 trispecific trimerbody ATTACKICB, for the treatment of solid tumors.
Learning Objectives:
At the completion of this activity, participants will know
improve the clinical applicability of T-cell engaging antibodies through in situ mRNA delivery.
evaluate pharmacokinetics and therapeutic potential of mRNA-encoded bi- or trispecific antibodies.
examine RNA nanocarrier structure using advanced complementary characterization techniques.
Ivana Zagorac – PhD, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.; Marta Compte – MD, PhD, Leadartis SL, Madrid, Spain.; Marianna Gerina – PhD, Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, Switzerland.; Bruno Silva – PhD, Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, Switzerland.; Luis Álvarez-Vallina – MD, PhD, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.; María José Alonso Fernández – PhD, University of Santiago de Compostela, Santiago de Compostela, Spain.
