Abstract 3917: Developing new anti-Trop2-antibody-based therapies and optical imaging modalities for epithelial cancers.

Abstract Carcinomas, which arise from epithelial tissues, account for 80 to 90 percent of all cancer cases and remain a major clinical challenge. Trophoblastic cell surface antigen-2 (Trop-2) is a transmembrane glycoprotein widely overexpressed in nearly all epithelial cancers. The strong association of elevated Trop-2 with metastasis and poor patient outcomes highlights Trop-2 as a compelling therapeutic and diagnostic target. Here, we report the development of a new class of highly specific human antibodies targeting Trop-2 that represents a promising approach for the development of novel therapeutic and imaging strategies in Trop-2-positive carcinomas. Our lead anti-Trop-2antibodies exhibit high binding affinity and specificity. The anti-Trop-2 antibodies demonstrate potent antitumor activity in vivo, significantly delaying tumor progression and suppressing metastasis in pre-clinical models of breast and lung cancers. Importantly, no detectable toxicity was observed in animals receiving anti-Trop-2 antibodies. To enable real-time detection of Trop-2-expressing tumors, we engineered an optical imaging agent by conjugating our lead anti-Trop-2 antibody to ICG. These antibody-ICG-conjugates robustly visualized Trop-2-positive lesions with a high positive-to-negative tumor contrast ratio and enabled precise surgical guidance during lymph node resection. Collectively, we have developed a new series of anti-Trop-2 antibodies that can be utilized as therapeutic and optical imaging agents, establishing a strong foundation for the translational development of targeted interventions for Trop-2-positive carcinomas. Citation Format: Tanya Stoyanova.. Developing new anti-Trop2-antibody-based therapies and optical imaging modalities for epithelial cancers [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 3917.