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Detection of multiple CEACAM antigens to enhance visualisation of colorectal PDOX tumours

Wed, 02/12/2020 - 10:18
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Researchers from the Department of Surgery and the Moores Cancer Center at the University of California in La Jolla California and the VA San Diego Healthcare System in San Diego, CA, have tested a novel anti-CEACAM antibody conjugated to a fluorescent dye for detection of multiple CEACAM antigens to enhance visualisation of colorectal PDOX tumours and metastases in murine models.

The research team's aim was to investigate mAb 6G5j binding characteristics and to validate fluorescence targeting of colorectal tumours and metastases in patient derived orthotopic xenograft models with fluorescently labelled 6G5j. The outcomes, ‘Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models’, were published in the journal Oncotarget.

Anti-CEACAM antibody 6G5j binds multiple CEACAMs which may lead to improved detection of tumour margins for tumours 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.

In the study, nude mice received orthotopic implantation of patient-derived primary colon cancer and patient-derived colon cancer metastases.

"Early diagnosis and surgical resection of a wide variety of epithelial malignancies remain a vital challenge due to difficulty of intraoperative recognition of tumour margins and small metastases during minimally invasive procedures,” said Dr Michael Bouvet from the Moores Cancer Center and VA San Diego Healthcare System in San Diego.

While immune cells and endothelium solely express CEACAM1, human epithelial cells show a much more complex CEACAM expression pattern. CEACAM1, CEACAM5 and CEACAM6 are co-expressed in epithelial cells of the gastro-intestinal tract and can also be over-expressed in endometrial, lung, ovarian, cervical, breast and colon cancers.

Prior studies have successfully utilized fluorescently-labelled antibodies in mouse models to specifically visualize pancreatic and colorectal tumours.

While anti-CEA antibodies conjugated to fluorophores have enabled tumour visualisation, the simultaneous targeting of multiple antigens may further enhance visualization, provide more distinct tumour margins and improve detection of metastases.

The Bouvet Research Team concluded that since this mAb binds to multiple antigens that are commonly present in colon tumors, namely CEACAM1, 5 and 6, it may provide improved detection of cancer margins for tumors with variable expression of CEA and other CEACAMs. Further studies are necessary to validate the use of 6G5j-IR800CW in human patients with colorectal cancer.

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