BCCMA: VA Colorectal Cancer Clinical & Computational Collaborative (VA-5C): NIR-labeled antibodies to target and label colon polyps and cancer for improved diagnosis and surgery

Va San Diego Healthcare System, San Diego CA

Investigators

Abstract

Colorectal cancers comprise the third most common cause of cancer-related death in the US and are major causes of death in the Veteran population. For colorectal cancer, early detection and complete surgical resection of tumors are critical to patient outcomes. The present application aims to develop a tumor-targeting fluorescent antibody that will specifically label premalignant polyps and primary and metastatic colon cancer to increase the accuracy of diagnosis and treatment and improve outcomes. With their unique properties, anti-mucin antibodies show great promise as targeting moieties in molecular imaging and therapy. Their fast blood clearance, rapid and homogenous tissue penetration, and low background retention allow highly specific imaging at early time points after administration and effective therapy with minimal nonspecific toxicity, as demonstrated by our published feasibility studies. Our published feasibility experiments have demonstrated that near-infrared (NIR) fluorophore-labeled antibodies against tumor-specific antigens will improve visualization, detection, resection, and outcome of colorectal cancer in genetically engineered mouse models (GEMMs) and patient-derived orthotopic xenograft (PDOX) mouse models, which mimic the clinical behavior of cancers. The present application will accomplish the necessary experiments for the NIR-labeled antibodies to be ready for clinical development. Our proposal has the following aims: 1) NIR-labeled antibodies will be evaluated and compared to control antibodies for their ability to target and illuminate premalignant colon polyps in GEMMs for fluorescence colonoscopy and 2) NIR-labeled antibodies will be evaluated and compared to control antibodies for their ability to target and illuminate primary and metastatic colon cancer in PDOX models for fluorescence-guided surgery (FGS). Achievement of the goals of this application will establish fluorescent tumor-specific antibodies that brightly label tumors and metastases in patient like mouse models of colorectal cancer that are demonstrated to be effective for FGS. Therefore, by the end of the funding period, the NIR-labeled antibody will be used ready for clinical development. The fluorescent-labeled tumor-specific antibodies developed in this application will be used to improve the outcome of the Veteran population with colorectal cancer. Grant application features: · Tumor-specific anti-mucin antibodies for labeling of premalignant polyps and colorectal cancer · Very bright tissue penetrating NIR dyes · PDOX mouse models targeting recalcitrant colorectal cancer · Near-infrared fluorescence guided colonoscopy and surgery