Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer

Abstract

Tumour-specific antigens have been an area of interest in cancer therapy since their discovery in the middle of the 20th century. In the era of immune-based cancer therapeutics, redirecting our immune cells to target these tumour-specific antigens has become even more relevant. Cancer-testis antigens (CTAs) are a class of antigens with an expression specific to the testis and cancer cells. CTAs have also been demonstrated to be expressed in a wide variety of cancers. Due to their frequency and specificity of expression in a multitude of cancers, CTAs have been particularly attractive as cancer-specific therapeutic targets. There is now a rapid expansion of CTAs being identified and many studies have been conducted to correlate CTA expression with cancer and therapy-resistant phenotypes. Furthermore, there is an increasing number of clinical trials involving using some of these CTAs as molecular targets in pharmacological and immune-targeted therapeutics for various cancers. This review will summarise the current knowledge of the biology of known CTAs in tumorigenesis and the regulation of CTA genes. CTAs as molecular targets and the therapeutic implications of these CTA-targeted anticancer strategies will also be discussed.

Keywords: CT antigens; cancer; cancer-testis antigens.

Figure 1

Shared characteristics between tumorigenesis and embryogenesis and spermatogenesis. During the transition from normal to tumour and metastasis (top panel), cancer cells acquire many characteristics highly similar to those present during normal development (bottom panel) when the zygote develops into an embryo and during the spermatogenesis process.

Figure 2

The hallmarks of cancer and examples of CTAs associated with each hallmark. In the latest update of the hallmarks of cancer, one can find examples of the involvement of CTAs in almost every hallmark, from original to newly emerging hallmarks.

Figure 3

Pictorial summary of our current knowledge on how cancer-testis antigen (CTA) expression is regulated in the context of cancer.

Figure 4

Pie charts indicating the proportion of current therapeutic strategies in completed and active clinical trials targeting CTAs. A gradual shift in the trend from more vaccine-based strategies to T-cell-based strategies is evident from the increase in the proportion of active trials that utilises T-cell-based strategies compared to earlier completed trials.(Information was obtained from https://clinicaltrials.gov, 6 March 2023).