Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models
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Hannah M. Hollandsworth1,2,5, Siamak Amirfakhri1,2,5, Filemoni Filemoni1,2,5, Verena Schmitt3, Gunther Wennemuth3, Alexej Schmidt6, Robert M. Hoffman1,2,4,5, Bernhard B. Singer3,* and Michael Bouvet1,2,5,*
1 Department of Surgery, University of California, La Jolla, CA, USA
2 Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
3 Institute of Anatomy, University Hospital, University Duisburg-Essen, Essen, Germany
4 AntiCancer, Inc., San Diego, CA, USA
5 VA San Diego Healthcare System, San Diego, CA, USA
6 Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
* These authors contributed equally to this work
Keywords: carcinoembryonic antigen; CEACAM; colon cancer; fluorescence; near-infrared
Received: September 25, 2019 Accepted: January 04, 2020 Published: January 28, 2020
Background: Monoclonal antibody (mAb) 6G5j is a novel anti-CEACAM monoclonal antibody. Our aim was to investigate mAb 6G5j binding characteristics and to validate fluorescence targeting of colorectal tumors and metastases in patient derived orthotopic xenograft (PDOX) models with fluorescently labeled 6G5j.
Materials/Methods: The MAb 6G5j binding profile was analyzed with ELISA, Western blot and immunohistochemistry. MAb 6G5j was conjugated to near-infrared dye IR800CW (LI-COR). Western blotting was performed with various colon cancer cell lysates to determine CEACAM expression. Nude mice received orthotopic implantation of patient-derived primary colon cancer and patient-derived colon cancer metastases. Mice were administered varying doses of 6G5j-IR800CW via tail vein injection and imaged 24 and 48 hours later.
Results: MAb 6G5j bound to human CEACAM1, 3, 5, 6 and 8. Western blotting demonstrated varied expression of CEACAMs in 15 of 16 colon cancer lysates. Dose and time-response imaging demonstrated optimal imaging 48 hours after administration of 50 μg 6G5j-IR800CW (Tumor-to-liver ratio (TLR) 3.17, SEM ± 0.45). Primary cancers and multiple metastases were fluorescently visualized.
Conclusions: Anti-CEACAM antibody 6G5j binds multiple CEACAMs which may lead to improved detection of tumor margins for tumors and metastases that have variable expression of CEA and other CEACAMs. 6G5j mAb may be useful for colon cancer detection for pre-surgical diagnosis and fluorescence-guided surgery.
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