A T-Cell Engaging Bispecific Antibody With a Tumor-Selective Bivalent Folate Receptor Alpha Binding Arm for the Treatment of Ovarian Cancer

Authors

Brian C Avanzino
Kirthana Prabhakar
Pranjali Dalvi
Sharon Hartstein
Hannes Kehm
Aarti Balasubramani
Andrew A Boudreau
Ben Buelow
Karen Chang
Laura M Davison
Suhasini Iyer
Vidyut Kalwit
Kristin Lewis Wilson
Harbani K Malik-Chaudhry
Will Pierson
Geovanni Pineda
Udaya S Rangaswamy
Sowmya Saiganesh
Ute Schellenberger
Harshad S Ugamraj
Rodolfovan D Yabut
Roland Buelow
Jocelyn Chapman
Nathan D Trinklein
Katherine E Harris

Publication Date

1-1-2022

Journal

OncoImmunology

Abstract

The use of T-cell engagers (TCEs) to treat solid tumors is challenging, and several have been limited by narrow therapeutic windows due to substantial on-target, off-tumor toxicities due to the expression of low levels of target antigens on healthy tissues. Here, we describe TNB-928B, a fully human TCE that has a bivalent binding arm for folate receptor alpha (FRα) to selectively target FRα overexpressing tumor cells while avoiding the lysis of cells with low levels of FRα expression. The bivalent design of the FRα binding arm confers tumor selectivity due to low-affinity but high-avidity binding to high FRα antigen density cells. TNB-928B induces preferential effector T-cell activation, proliferation, and selective cytotoxic activity on high FRα expressing cells while sparing low FRα expressing cells. In addition, TNB-928B induces minimal cytokine release compared to a positive control TCE containing OKT3. Moreover, TNB-928B exhibits substantial

Keywords

Bispecific antibody, T-cell engager, folate receptor alpha, ovarian cancer, on-target, off-tumor toxicity