Cancer-Testis Antigens and Immunotherapy in the Light of Cancer Complexity

Abstract

The ability of immunotherapy to evoke successful antitumor immune responses has been well documented over the past decade. Despite abundant preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of the drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as a viable alternative to traditional therapies for treatment of various cancers. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy is hindered by several factors. Among these are the paucity of tumor-associated antigens (TAA) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. Indeed, such adverse effects, which can be immunological and/or parenchymal, can be particularly severe and even fatal to some patients. A family of TAA called cancer-testis antigens (CTA) has been identified and their encoding genes have been extensively investigated. CTA expression has been demonstrated in a variety of human cancer tissues, and at least 19 CTA have been found to elicit humoral and/or cellular immune responses in cancer patients. Here we discuss how CTA and immunotherapy will most likely play a major role in the cure of cancer in the light of cancer complexity.

Systematic analysis of genetic variants in cancer-testis genes identified two novel lung cancer susceptibility loci in Chinese population

“…Although lung cancer GWASs have identified dozens of lung cancer susceptibility loci, more lung cancer associated variants remained to be identified [3]. Cancer-testis genes were recognized as promising therapeutic targets for cancers due to their high immunogenicity in tumor tissues [22,23]. However, the roles of genetic variants in CT genes in the development of lung cancer have not been revealed in previous studies.…”

Cancer‐testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities

“…Indeed, a number of cancer vaccine clinical trials are ongoing . Although some studies seem promising, a number of possible limitations in using CT antigens in targeted immunotherapy are yet to be overcome Merkel cell carcinoma (MCC) is a neuroendocrine tumor of the skin that behaves aggressively, with a 5‐year survival rate of only 18% in metastatic disease .…”

Serum levels of anti‑sperm‑associated antigen 9 antibody are elevated in patients with hepatocellular carcinoma

“…The expression of these antigens is normally restricted to the testis, but these antigens are also expressed (22)(23)(24). Several studies have revealed that CTAs are highly expressed in the tumor tissue of patients with HCC (25)(26)(27).…”

“…SPAG9 belongs to the c-Jun-NH 2 terminal kinase-interacting protein family (28). Proteins from this family function in cell growth, proliferation, apoptosis and tumor development (29,30), and are expressed in renal cell carcinoma, and ovarian, cervical, breast, thyroid and colorectal cancer tissues, SPAG9 provokes a strong humoral immune response, and its autoantibody can be detected in the peripheral blood of patients with the aforementioned types of cancer (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). The current study hypothesized that anti-SPAG9 antibody may be detected in the peripheral blood of patients with HCC, and that, in combination with serum AFP levels, it may provide a reliable diagnostic test for HCC, particularly for AFP-negative patients.…”