Abstract 2454: In vivo binding of chTNT-1/B antibodies (Cotara) to DNA/histone complexes in tumors using near-infrared optical imaging

Abstract

Abstract Tumors contain both microscopic and macroscopic areas of necrotic cells. These have abnormal cell membrane permeability, which allows passage of large macromolecules such as antibodies into the cell. 131I-chTNT-1/B antibody (Cotara) is a novel, single administration agent designed to target tumor necrosis that has completed a Phase II clinical trial for recurrent glioblastoma multiforme (GBM), showing 9.3 month median overall survival for patients. Since 131I-chTNT-1/B antibody is a high-molecular-mass protein, it cannot easily pass from the systemic circulation through the blood-brain barrier (BBB) and thus can only be delivered locally by an intratumoral catheter. We have developed a human ME-180 cervical carcinoma xenograft tumor model in nude mice to characterize the targeting of chTNT-1/B to necrotic areas using near infrared (NIR) optical imaging. The use of NIR optical imaging is a powerful translational tool to monitor in vivo antibody targeting. chTNT-1/B was labeled with a NIR fluorescent dye and kinetics of antibody retention in tumors was measured by NIR optical imaging following intratumoral injection of the NIR-chTNT-1/B. NIR-chTNT-1/B was retained in ME180 tumors for a longer duration compared to NIR dye alone. Labeling of chTNT-1/B with a low dye/protein ratio was necessary to demonstrate maximum specific targeting to tumor necrosis. Evaluation of in vivo antibody targeting to tumors using NIR imaging may facilitate improvements for treatment of patients with malignant glioma with Cotara. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2454. doi:1538-7445.AM2012-2454