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Research Article: The significance of CEACAM60, a carcinoembryonic antigen (CEA) homolog, as a tumor antigen in the porcine cancer model

Date Published: 2026-05-13

Abstract:
Translational medicine remains one of the central challenges in modern biomedical research. A major bottleneck in this field is the limited availability of suitable animal models that reliably predict human disease outcomes. Large animal models, particularly pigs, are increasingly recognized as promising preclinical systems for translating fundamental immunological and oncological discoveries into clinically relevant applications. Given the pivotal role of the carcinoembryonic antigen (CEA) family, both as key regulators of immune responses (e.g., CEACAM1) and as tumor antigens (e.g., CEA) in humans, we performed a comprehensive characterization of the porcine CEA gene family. By generating monoclonal antibodies specific for individual porcine CEACAMs, we analyzed the expression of porcine CEACAMs in tissues and culture supernatants. Our analyses identified the ortholog of CEACAM1 as well as a GPI-anchored CEACAM (CEACAM60), a homolog of human CEA. We demonstrated that CEACAM1 is expressed on various immune cell populations, consistent with patterns observed in humans. Furthermore, we found that CEACAM60 is selectively expressed at the apical membrane of enterocytes in the large intestine, mirroring the expression topology described for human CEA. Strict apical localization in healthy epithelial tissues results in the release of CEACAM60 into the intestinal lumen, thereby preventing its presence in systemic body fluids. In contrast, in malignant tissues, loss of cellular differentiation and disruption of apical-basal polarity abolish this compartmentalization, providing the essential prerequisite for the occurrence of CEACAM60 in serum under neoplastic conditions. Based on these findings, we developed a detection assay for CEACAM60 in fluids, which could serve as a basis for dynamic monitoring of tumor progression in animals in the future. Considering the central roles of CEACAM1 and CEA in tumor immunotherapy and tumor surveillance in humans, porcine models with an increased predisposition for colorectal neoplasia may provide a valuable translational platform for the development and refinement of next-generation colorectal cancer immunotherapies.

Introduction:
Murine models, especially when they were genetically modified, have proven to be very useful to understand the mechanism of certain human diseases ( 1 ). However, in certain circumstances, murine models are not sufficient to optimize new diagnostic and therapeutic approaches ( 2 ). Frequently, the size and anatomy of the model animal are critical constrains, but sometimes also the physiology of humans exclude mice or rodents as adequate model organisms. Thus, there is a clear need for alternative animal models.…

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