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Review
. 2010 May;6(5):717-32.
doi: 10.2217/fon.10.36.

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

Stacey N Akers  1 , Kunle Odunsi, Adam R Karpf
Affiliations
Review

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

Stacey N Akers et al. Future Oncol. 2010 May.

Abstract

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.

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Figures

Figure 1
Figure 1. Cancer germline antigen gene regulation in human cancer
CG: Cancer germline; FGFR: FGF receptor; MBD: Methyl-CpG-binding domain proteins; me: Methylation.
Figure 2
Figure 2. Epigenetic therapy augmentation of cancer germline antigen immunotherapy
CG: Cancer germline; DNMTi: DNA methyltransferase inhibitors; DZnep: 3-deazaneplanocin A; EZH2i: Enhancer of zeste homolog 2 inhibitors; HDACi: Histone deacetylase inhibitors; HMTi: Histone methyltransferase inhibitors.
See this image and copyright information in PMC

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