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Identification of a MHC class-II restricted epitope in carcinoembryonic antigen

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Purpose

The carcinoembryonic antigen (CEA) is extensively expressed on the vast majority of colorectal, gastric, and pancreatic carcinomas, and, therefore, is a good target for tumor immunotherapy. CD4+ T-helper (Th) cells play a critical role in initiation, regulation, and maintenance of immune responses. In this study, we sought to identify Th epitopes derived from CEA which can induce CEA-specific Th responses. The combined application with cytotoxic T lymphocyte (CTL) epitopes would be more potent than tumor vaccines that primarily activate CTL alone.

Methods

We utilized a combined approach of using a computer-based algorithm analysis TEPITOPE and in vitro biological analysis to identify Th epitopes in CEA.

Results

Initial screening of healthy donors showed that all five predicted peptides derived from CEA could induce peptide-specific T-cell proliferation in vitro. We characterized these CEA epitopes by establishing and analyzing peptide-specific T-cell clones. It was shown that CD4+ T-cells specific for the CEA116 epitope can recognize and respond to naturally processed CEA protein and CEA116 epitope can be promiscuously presented by commonly found major histocompatibility complex (MHC) alleles. Furthermore, it was demonstrated that immunization of human leukocyte antigen (HLA)-DR4 transgenic mice with CEA116 peptide elicited antigen-specific Th responses which can recognize the antigenic peptides derived from CEA protein and CEA-positive tumors.

Conclusion

The MHC class II-restricted epitope CEA116 could be used in the design of peptide-based tumor vaccine against several common cancers expressing CEA.

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Acknowledgements. We thank J. Zhang for his expert advice, L. Rollins for technical assistance, and volunteers for donating their blood. This work was supported by grants from the U.S. Army Breast Cancer Research Program BC990963 (X.F.H.) and NIH AI48711 (S.Y.C.). This work was also supported in part by MithraGen Inc.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Alkek Bldg. N1004, Houston, TX, 77030, USA

    Lei Shen, Roland Schroers, Xue F. Huang & Si-Yi Chen

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Lei Shen, Roland Schroers & Si-Yi Chen

  3. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Xue F. Huang

  4. Vaccinome, Kearny, NJ, USA

    Juergen Hammer

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  1. Lei Shen
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Correspondence to Si-Yi Chen.

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Shen, L., Schroers, R., Hammer, J. et al. Identification of a MHC class-II restricted epitope in carcinoembryonic antigen. Cancer Immunol Immunother 53, 391–403 (2004). https://doi.org/10.1007/s00262-003-0455-y

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