Abstract 2380: Fluorescence labeling of human gastric cancer using novel tumor specific near infrared labeled antibodies

Abstract

Introduction: Gastric cancer has a global incidence of ~1 million cases per year. Currently, complete surgical resection is the only opportunity for cure for patients. Bright labeling of tumor margins with tumor specific markers could improve outcomes. This report demonstrates the advantages of targeting gastric cancer with humanized anti-CEA and TAG-72 antibodies in mouse models. Methods: A cell line of human gastric cancer, MKN45, and a patient-derived tumor, KG8, were used to create xenograft models. To establish orthotopic models for each, ~1mm tumor fragments were harvested from subcutaneous models of these lines and sutured to the lesser curvature of the stomach. Humanized versions of TAG-72 (huCC44) and CEA (M5A) were conjugated to the near infrared dye IRDye800CW. IgG was conjugated to IRDye800CW and used as a control. For CEA-IR800 and IgG-IR800, mice received 50 µg IV and were imaged after 72 hours. For Tag72-IR800, mice received 75 µg IV and were imaged after 96 hours. Fluorescence imaging was performed on the mice using the LI-COR Pearl Imaging System. A tumor to background ratio (TBR) was calculated by dividing mean fluorescence intensity of the tumor versus normal gastric tissue. Results: Humanized anti-CEA and TAG-72 brightly labeled multiple mouse models of human gastric cancer (Table 1). The TBR for TAG-72 labeling of KG8 was 2.777. CEA had a superior TBR of 3.528 compared to 0.606 for the control (IgG) in KG8 models. In MKN models labelled with CEA, an excellent average TBR of 7.407 were seen compared to 0.668 for the control. Conclusion: Humanized anti-CEA and TAG-72 antibodies conjugated to near-infrared fluorescent dyes provide specific labeling of gastric cancers in orthotopic models. These tumor-specific fluorescent antibodies are promising potential clinical tools for visualization of gastric cancer margins at the time of surgical resection and improved surgical outcomes. Orthotopic Model Antibody Tumor to Background Ratio KG8 anti-TAG-72 2.777 KG8 anti-CEA 3.528 KG8 Control 0.606 MKN anti-CEA 7.407 MKN Control 0.668 Citation Format: Kristin E. Cox, Michael A. Turner, Siamak Amirfakhri, Thinzar M. Lwin, Pradipta Ghosh, Marygorret Obonyo, Kaitlyn M. Kelly, Robert M. Hoffman, Paul J. Yazaki, Michael Bouvet. Fluorescence labeling of human gastric cancer using novel tumor specific near infrared labeled antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2380.