What question did this study set out to answer?

This research aims to explore the effectiveness of a bispecific antibody targeting FOLR1 and TRAIL-R2 in inducing apoptosis in ovarian cancer cells.

April 5, 2026

Abstract 4656: A Novel FOLR1 and TRAIL-R2 targeting bispecific antibody to treat ovarian cancer

Key Points

This research aims to explore the effectiveness of a bispecific antibody targeting FOLR1 and TRAIL-R2 in inducing apoptosis in ovarian cancer cells.
Developed TRAILBody targeting FOLR1 and TRAIL-R2.
Conducted in vitro and in vivo analyses across ovarian cancer cell lines and patient-derived xenografts.
Compared TRAILBody against Elahere and monospecific TRAIL-R2 antibody agonists for efficacy and safety.
Investigated mechanisms of receptor clustering and activation related to apoptosis.
TRAILBody demonstrated superior apoptosis induction compared to Elahere in ovarian cancer models.
Significant tumor-specific apoptosis independent of traditional mediators was observed.
Enhanced receptor oligomerization led to rapid caspase-3 activation and strong cell death effects.
Minimized off-target toxicity and improved safety profile, particularly in cisplatin-resistant models.

Abstract

Abstract We report a first-in-class tumor antigen dependent apoptotic inducing bispecific antibody, TRAILBody™, that co-targets FOLR1 and TRAIL-R2, selectively inducing TRAIL-R2 mediated apoptotic cell death with superior selectivity and efficacy. In a head-to-head comparison with the recently approved ADC drug, Elahere, FOLR1 TRAILBody showed superior activity. Extensive in vitro and in vivo analyses across ovarian cancer cell lines, patient-derived xenografts (PDX), and murine models demonstrate that FOLR1 TRAILBody drive high-level tumor-specific apoptosis independent of ADCC, significantly overcoming limitations of FcγR-mediated TRAIL-R2 clustering. Mechanistically, FOLR1 functions as a clustering anchor for TRAIL-R2, yielding enhanced receptor oligomerization, rapid caspase-3 activation, and robust cell death in FOLR1+ ovarian cancer models. Preclinical models confirm optimal stability, avidity, and selective tumor localization with minimized off-target toxicity. Notably, FOLR1 TRAILBody show superior regression of cisplatin-resistant PDX tumors and improved safety profile compared to clinically tested monospecific TRAIL-R2 antibody agonists, including minimized liver accumulation and hepatotoxicity with reduced levels of AST/ALT in blood. This study reveals a previously unappreciated mechanism in antibody therapeutics: the use of a tumor-enriched anchor (FOLR1) to optimize death receptor clustering and activation, enabling a quantum leap in apoptotic signaling and therapeutic index for ovarian cancer. The TRAILBody platform thus offers a foundation for next-generation immuno-oncology agents and revives hope for the clinical translation of death receptor agonism, particularly in solid tumors marked by immune exclusion and therapeutic resistance. Citation Format: Shiva Bhowmik, William Brady. A Novel FOLR1 and TRAIL-R2 targeting bispecific antibody to treat ovarian cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4656.

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