P83: Primary and Metastatic Gastric Cancers in Patient-derived Orthotopic Xenografts Brightly Labeled by Fluorescent anti-CEA Antibody

Friday, March 24, 2023

12:41 PM – 12:46 PM

Location: SSO HUB Pan-Tumor Zone: CRS, HPB, Pan-Tumor & Upper GI

Poster Presenter(s)

Kristin Cox, MD

Resident Physician
Department of Surgery, University of California San Diego
San Diego, California, United States

Disclosure information not submitted.

Author(s)

Kristin Cox, MD

Resident Physician
Department of Surgery, University of California San Diego
San Diego, California, United States

Disclosure information not submitted.
Michael A. Turner, MD

Surgery resident
University of California, San Diego
San Diego, California, United States

Disclosure information not submitted.
SA

Siamak Amirfakhri, PhD

Post-doctoral Research Scientist
VA San Diego Healthcare System, United States

Disclosure information not submitted.
TL

Thinzar Lwin, MD

Associate Professor of Surgery
City of Hope National Medical Center, Duarte, CA, United States, United States

Disclosure information not submitted.
PG

Pradipta Ghosh, MD

Professor
Department of Cellular and Molecular Medicine, University of California San Diego, United States

Disclosure information not submitted.
MO

Marygorret Obonyo, MD

Associate Professor
Department of Medicine, University of California San Diego, United States

Disclosure information not submitted.
KK

Kaitlyn Kelly

Disclosure information not submitted.
RH

Robert Hoffman, PhD

Scientist
AntiCancer Inc., United States

Disclosure information not submitted.
PY

Paul Yazaki, PhD

Research Professor
Department of Immunology and Theranostics, Beckman Research Institute of the City of Hope, United States

Disclosure information not submitted.
MB

Michael Bouvet, MD

Professor
Department of Surgery, University of California San Diego, United States

Disclosure information not submitted.

Introduction: R1 resection of gastric cancer drastically reduces 5-year survival to 13% compared to 60% for R0. Improved visualization of tumor margins with bright labeling of tumor specific markers could improve outcomes. This report demonstrates the advantages of targeting gastric cancer with a humanized anti-CEA antibody in patient-derived mouse models.

Methods: Patient derived xenografts, KG8 and KG10, were established from two patients who underwent gastrectomy. To create patient-derived orthotopic xenografts (PDOX) of KG8, tumor fragments were implanted into the greater curve of the stomach using a technique of surgical orthotopic implantation. For tumor labeling, M5A (humanized anti-CEA) antibodies, or IgG as a control, were conjugated with the near infrared dye IRDye800CW. Subcutaneous models received 50 µg M5A-IR800 (KG8 and KG10) or 50 µg IgG control (KG8 alone) and were imaged daily for 96 hours. For KG8 PDOX models, mice received 50 µg of M5A-IR800 or 50 µg IgG control and were imaged after 72 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 background tissue.

Results: M5A-IR800 administration resulted in bright labeling of KG8 and K10 subcutaneous tumors and KG8 PDOX tumors. In subcutaneous models labeled with M5A-IR800, increasing TBRs were seen up to 3.90 (±0.98) for KG8 and 4.76 (±1.78) for KG10 at 96 hrs, while the control group (IgG-IR800) showed TBRs of only 0.87 (±0.086). In the KG8 PDOX models, the TBR was 3.52 compared to 0.606 for the IgG control (Figure 1). Additionally, abdominal wall metastasis in the PODX models showed robust labeling with a TBR of 8.91 for M5A-IR800 compared to 1.46 for IgG control. Chart review revealed the source patients for KG8 and KG10 had serum CEA levels within 1 month of surgery that were 176 and 5.7 respectively, suggesting that significantly elevated serum CEA level are not necessary to achieve bright labeling with anti-CEA antibodies.

Conclusions: Humanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide specific labeling of gastric cancers in PDOX models for both the primary and metastatic tumors. Serum CEA levels near time of surgery however did not influence tumor labeling after transplantation to mice. This tumor-specific fluorescent antibody is a promising potential clinical tool for improving gastric cancer resection margins.

Learning Objectives:

Recognize the need for improved tools for surgical resection of gastric cancers.
Critically appraise a fluorescent antibody's ability to label gastric tumors.
Understand the role of fluorescent labeling of tumors for improved visualization at time of surgical resection.