Cancer testis antigen subfamilies: Attractive targets for therapeutic vaccine (Review)

Abstract

Cancer‑testis antigen (CTA) is a well‑accepted optimal target library for cancer diagnosis and treatment. Most CTAs are located on the X chromosome and aggregate into large gene families, such as the melanoma antigen, synovial sarcoma X and G antigen families. Members of the CTA subfamily are usually co‑expressed in tumor tissues and share similar structural characteristics and biological functions. As cancer vaccines are recommended to induce specific antitumor responses, CTAs, particularly CTA subfamilies, are widely used in the design of cancer vaccines. To date, DNA, mRNA and peptide vaccines have been commonly used to generate tumor‑specific CTAs in vivo and induce anticancer effects. Despite promising results in preclinical studies, the antitumor efficacy of CTA‑based vaccines is limited in clinical trials, which may be partially attributed to weak immunogenicity, low efficacy of antigen delivery and presentation processes, as well as a suppressive immune microenvironment. Recently, the development of nanomaterials has enhanced the cancer vaccination cascade, improved the antitumor performance and reduced off‑target effects. The present study provided an in‑depth review of the structural characteristics and biofunctions of the CTA subfamilies, summarised the design and utilisation of CTA‑based vaccine platforms and provided recommendations for developing nanomaterial‑derived CTA‑targeted vaccines.

Keywords: cancer vaccine; cancer‑testis antigen; gene family; melanoma antigen; nanomaterial delivery system; synovial sarcoma X.

Figure 1

General information of cancer-testis antigen subfamilies: MAGE, SSX, GAGE, XAGE, PAGE and NY-ESO-1. Chromosome localization, expression pattern and biofunction in malignancies were briefly illustrated. MAGE, melanoma antigen; SSX, synovial sarcoma X; GAGE, G antigen.

Figure 2

Schematic illustration of cancer-testis antigen-based cancer vaccine therapy. The general process of different types of cancer vaccine exerting their anti-tumor effects. Challenges of DNA vaccine, mRNA vaccine, peptide vaccine and nano vaccine were also indicated. APC, antigen-presenting cells; CTL, cytotoxic T lymphocyte; TCR, T-cell receptor; MHC, major histocompatibility complex; TME, tumor microenvironment; MAGE, melanoma antigen; SSX, synovial sarcoma X; HAGE, H antigen; IMP3, insulin-like growth factor II mRNA-binding protein 3; TTK, TTK protein kinase.

Figure 3

Pie charts of (A) cancers treated with CTA-based vaccines in clinical trials and (B) CTAs utilized to design cancer vaccines in clinical trials. HNSCC, head and neck squamous cell carcinoma; MAGE, melanoma antigen; CTA, cancer-testis antigen; LY6K, lymphocyte antigen 6 complex locus K; URLC10, up regulating lung cancer 10 gene; PRAME, PRAME nuclear receptor transcriptional regulator; TTK, TTK protein kinase; IMP-3, insulin-like growth factor II mRNA-binding protein 3; sp17, sperm protein-17.