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Cancer/testis antigens and urological malignancies

Nature Reviews Urology volume 9, pages 386–396 (2012)Cite this article

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Abstract

Cancer/testis antigens (CTAs) are a group of tumour-associated antigens (TAAs) that display normal expression in the adult testis—an immune-privileged organ—but aberrant expression in several types of cancers, particularly in advanced cancers with stem cell-like characteristics. There has been an explosion in CTA-based research since CTAs were first identified in 1991 and MAGE-1 was shown to elicit an autologous cytotoxic T-lymphocyte (CTL) response in a patient with melanoma. The resulting data have not only highlighted a role for CTAs in tumorigenesis, but have also underscored the translational potential of these antigens for detecting and treating many types of cancers. Studies that have investigated the use of CTAs for the clinical management of urological malignancies indicate that these TAAs have potential roles as novel biomarkers, with increased specificity and sensitivity compared to those currently used in the clinic, and therapeutic targets for cancer immunotherapy. Increasing evidence supports the utilization of these promising tools for urological indications.

Key Points

  • Restricted expression of cancer/testis antigens (CTAs) in an immune-privileged organ (the adult testis) and aberrant expression in malignant tissue make CTAs ideal biomarkers and immunotherapeutic targets for managing urological cancers

  • Unlike many cancer-associated genes, which frequently harbour mutations associated with their pathological function, mutations in genes encoding the CTAs are extremely rare

  • The majority of CTAs are thought to be intrinsically disordered proteins that often engage in promiscuous interactions with other proteins when overexpressed

  • A key problem for CTA-based therapies is tumour cell heterogeneity, which results in differential expression of CTAs; use of the FDA-approved DNA methylation inhibitor decitabine can circumvent this issue

  • Use of a combination of markers is likely to improve the accuracy of prognostication and treatment stratification compared to utilization of a single marker

  • The success of clinical trials underscores the immunotherapeutic potential of a CTA-based approach and indicates that CTAs could be used as clinical tools for urological malignancies in the near future

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Figure 1: Schematic diagram of an immunotherapeutic approach to treating urological malignancies that utilizes immunogenic peptides corresponding to CTAs.
Figure 2: Normalized expression heat maps.
Figure 3: Schematic diagram of mammalian spermatogenesis that depicts the stages of testicular germ cell tumour development.

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Acknowledgements

This work was supported by a National Cancer Institute Specialized Program of Research Excellence, the Bernard L. Schwartz Scholar Award by the Patrick C. Walsh Cancer Research Fund, and the Patana Fund of the Brady Urological Institute.

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  1. James Buchanan Brady Urological Institute, 600 North Wolfe Street, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA

    Prakash Kulkarni, Takumi Shiraishi, Krithika Rajagopalan, Steven M. Mooney & Robert H. Getzenberg

  2. Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, 21218, MD, USA

    Robert Kim

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A provisional patent application covering an invention on a CTA-based gene signature for prostate cancer has been filed by Johns Hopkins University on behalf of P. Kulkarni, T. Shiraishi and R. H. Getzenberg.

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Kulkarni, P., Shiraishi, T., Rajagopalan, K. et al. Cancer/testis antigens and urological malignancies. Nat Rev Urol 9, 386–396 (2012). https://doi.org/10.1038/nrurol.2012.117

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