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Regulation of cancer germline antigen gene expression: implications for cancer immunotherapy

    Stacey N Akers

    Department of Gynecological Oncology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA

    ,
    Kunle Odunsi

    Departments of Gynecological Oncology & Immunology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA

    &
    Adam R Karpf

    † Author for correspondence

    Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA.

    Published Online:https://doi.org/10.2217/fon.10.36

    Cancer germline (CG; also known as cancer-testis) antigen genes are normally expressed in germ cells and trophoblast tissues and are aberrantly expressed in a variety of human malignancies. CG antigen genes have high clinical relevance as they encode a class of immunogenic and highly selective tumor antigens. CG antigen-directed immunotherapy is undergoing clinical evaluation for the treatment of a number of solid tumor malignancies and has been demonstrated to be safe, provoke immune responses and be of therapeutic benefit. Achieving an improved understanding of the mechanisms of CG antigen gene regulation will facilitate the continued development of targeted therapeutic approaches against tumors expressing these antigens. Substantial evidence suggests epigenetic mechanisms, particularly DNA methylation, as a primary regulator of CG antigen gene expression in normal and cancer cells as well as in stem cells. The roles of sequence-specific transcription factors and signal transduction pathways in controlling CG antigen gene expression are less clear but are emerging. A combinatorial therapeutic approach involving epigenetic modulatory drugs and CG antigen immunotherapy is suggested based on these data and is being actively pursued. In this article, we review the mechanisms of CG antigen gene regulation and discuss the implications of these mechanisms for the development of cancer immunotherapy approaches targeting CG antigens.

    Bibliography

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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