Cancer/testis antigens: an expanding family of targets for cancer immunotherapy

Abstract

Cancer/testis (CT) antigens are a category of tumor antigens with normal expression restricted to male germ cells in the testis but not in adult somatic tissues. In some cases, CT antigens are also expressed in ovary and in trophoblast. In malignancy, this gene regulation is disrupted, resulting in CT antigen expression in a proportion of tumors of various types. Since their initial identification by T-cell epitope cloning, the list of CT antigens has been greatly expanded through serological expression cloning (SEREX) and differential mRNA expression analysis, and approximately 20 CT antigens or antigen families have been identified to date. Characteristics commonly shared by CT antigens, aside from the highly tissue-restricted expression profile, include existence as multigene families, frequent mapping to chromosome X, heterogeneous protein expression in cancer, likely correlation with tumor progression, induction of expression by hypomethylation and/or histone acetylation, and immunogenicity in cancer patients. Spontaneous humoral and cell-mediated immune responses have been demonstrated against several CT antigens, including NY-ESO-1, MAGE-A, and SSX antigens. Since CT antigens are immunogenic and highly restricted to tumors, their discovery has led directly to the development of antigen-specific cancer vaccines, and clinical trials with MAGE-A and NY-ESO-1 are in progress.

NY‐ESO‐1/LAGE‐1 coexpression with MAGE‐A cancer/testis antigens: A tissue microarray study

“…1 Among healthy cells, both are almost exclusively expressed in germ cells at different maturation stages, whereas their expression is detectable in malignancies of different histological origin. Furthermore, both are encoded within chromosome X, albeit in regions distant from each other.…”

“…1 Among C/T antigens, NY-ESO-1 appears to play an important role since it is probably the most immunogenic member of the group and it is also capable to induce humoral responses in addition to specific cytotoxic T lymphocytes (CTL) and CD4þ T cells. 2,3 Remarkably, most recently a highly homologous determinant, LAGE-1, has been reported to be able to induce specific regulatory CD25þ/CD4þ in melanoma tumor infiltrating lymphocytes (TIL).…”

NY-ESO-1 (CTAG1B) expression in mesenchymal tumors

“…1 Cancer-testis antigens such as NY-ESO-1 have attracted increasing attention as immunotherapeutic targets because, among normal tissues, they are expressed only in adult testis germ cells and are atypically re-expressed in many malignancies. 2,3 NY-ESO-1 is of particular interest to researchers and clinicians because it is highly immunogenic and is expressed in a variety of carcinomas, melanomas, and sarcomas. 4 A recent clinical trial of adoptive immunotherapy, using genetically modified T cells directed against NY-ESO-1, demonstrated objective clinical responses in a number of metastatic synovial sarcoma and melanoma patients with NY-ESO-1-positive tumors.…”

Gene transfer approaches in cancer immunotherapy

“…Later, Lewis Thomas has demonstrated that the main cells involved in tumor elimination are cytotoxic T lymphocytes (CTLs). Today's knowledge about the broad spectrum of tumor antigens, recognized by the immune system 6,7 and main principles of immune surveillance, are actively used in development of antitumor immunotherapy. 8 However, a lot of mismatches and contradictions were found in Ehrlich's hypothesis.…”