Cancer-Testis Antigens in Canine Histiocytic Sarcoma and Other Malignancies (original) (raw)
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A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening
Proceedings of the National Academy of Sciences, 1997
Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.
Frontiers in Oncology
Editorial on the Research Topic Cancer testis antigens in cancer: Recent developments as cancer biomarkers and therapeutic targets Cancer testis antigens (CTAs) form a large family of proteins with highly restricted expression that is limited to male germ cells in the testis and trophoblast cells in the placenta. They are often re-expressed in tumors as a result of differential DNA methylation of their promoter regions, making them highly tumor-specific antigens. Moreover, CTAs are highly immunogenic as the immune system does not recognize them as self-proteins due to the immune privileged environment of the testis. Given their restricted expression patterns and immunogenic nature, CTAs have been identified as attractive candidate targets for anti-cancer therapy. This special issue was designed to highlight new advancements and insights into the oncogenic functions and biomarker or therapeutic potential of CTAs in cancer. CTAs have been implicated in diverse aspects of oncogenesis where individual CTAs have been shown to increase genomic instability, promote tumor growth, invasion and metastasis, impede apoptosis, and enhance angiogenesis (1). Here, Traynor et al. demonstrate that Synovial Sarcoma, X-breakpoint (SSX) proteins are implicated in biological processes that regulate tumor growth as well as metastasis. More specifically, they show that silencing of overall SSX expression reduces tumor growth and completely inhibits metastatic burden of lung and liver in vivo. Molecularly, they found that SSX silencing induces cell cycle stalling, increased apoptosis and reduced migration and invasion potential of melanoma cells. Of note, using the TCGA repository they show that all six protein-coding SSX members are expressed in melanomas with SSX1 and SSX2 Frontiers in Oncology frontiersin.org 01
Cancer-testis antigens: An update on their roles in cancer immunotherapy
Human Antibodies, 2019
BACKGROUND: Several recent studies have assessed suitability of tumor antigens for immunotherapy. Based on the restricted expression pattern in somatic tissues, cancer-testis antigens (CTAs) are possible candidates for cancer immunotherapy. These antigens are expressed in various tumors including gastrointestinal, breast, skin and hematologic malignancies. OBJECTIVES: To find clinical trials utilizing CTAs in cancer patients. METHODS: We searched PubMed, google scholar and specific websites that registers clinical trials. RESULTS: A number of clinical trials have been designed to evaluate safety and efficacy of CTA-based treatments. The results of some of them have been promising. In the current literature search, we summarized the clinical trials of CTA-based therapies in cancer patients. CONCLUSIONS: Based on the availability of different formulations of CTA-based vaccines, future researches should compare efficiency of these modalities.
Cancer/testis antigens and urological malignancies
Nature Reviews Urology, 2012
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.
Cancer-testis antigens: potential targets for cancer immunotherapy
Archives of Iranian medicine, 2009
Cancer-testis antigens are tumor antigens that their expression is almost limited to male germ cells in the testis. Some of cancer-testis antigens are also expressed in the ovary and in trophoblasts. Recently their expression has been seen in different types of tumors. Many pathophysiologic studies suggest that a blood-testis barrier exists in the testis. Because spermatogenesis begins at puberty, new cell-surface antigens are expressed when the immune system has refined the ability to distinguish self from nonself. So, sperms in the testis do not stimulate immune responses. In addition, although antigen-presenting cells are commonly seen in the interstitial spaces of the testis, these cells are scarcely seen within the seminiferous tubules. So, testis is considered as an immune-privileged site, and testis-specific genes, if expressed in cancers can be immunogenic. For this reason cancer-testis antigens are promising candidates for cancer immunotherapy and have become a major focus ...
Cancer-testis antigens: potential targets for cancer immunotherapy. Arch Iran Med
Archives of Iranian medicine
Cancer-testis antigens are tumor antigens that their expression is almost limited to male germ cells in the testis. Some of cancer-testis antigens are also expressed in the ovary and in trophoblasts. Recently their expression has been seen in different types of tumors. Many pathophysiologic studies suggest that a blood-testis barrier exists in the testis. Because spermatogenesis begins at puberty, new cell-surface antigens are expressed when the immune system has refined the ability to distinguish self from nonself. So, sperms in the testis do not stimulate immune responses. In addition, although antigen-presenting cells are commonly seen in the interstitial spaces of the testis, these cells are scarcely seen within the seminiferous tubules. So, testis is considered as an immune-privileged site, and testis-specific genes, if expressed in cancers can be immunogenic. For this reason cancer-testis antigens are promising candidates for cancer immunotherapy and have become a major focus for the development of vaccine-based clinical trials in recent years. In addition, these antigens can also be used as biomarkers for early detection of cancers.
Proceedings of the National Academy of Sciences, 2006
Cancer͞testis (CT) antigens are immunogenic proteins expressed in normal gametogenic tissues and in different types of tumors. CT antigens are promising candidates for cancer immunotherapy, and the identification of novel CT antigens is a prerequisite for the development of cancer vaccines. We have identified a CT antigen, named CTSP-1, with partial similarity to the breast differentiation antigen NY-BR-1. CTSP-1 presents several splicing and polyadenylation variants and has a very restricted expression pattern among normal tissues. CTSP-1 is exclusively expressed in normal testis and is aberrantly expressed in 47.6% (10 of 21) of tumor cell lines and in 44.4% (75 of 169) of tumors from different histological types. The highest percentages of positive expression were observed in melanomas (59.0%) followed by prostate (58.0%) and lung (57.0%) tumors. CTSP-1 is part of a highly conserved gene family, and members of this family also have a restricted expression pattern and similar protein structure. Antibodies against members of this gene family were detected in 10% (14 of 141) of plasma samples from patients with a wide spectrum of tumors. The highest percentages of antibody response were observed in patients with prostate (20.8%), thyroid (20.0%), and breast (16.6%) tumors. Because of its very restricted expression pattern in normal tissues and immunogenicity in different types of tumors, CTSP-1 should be considered a promising candidate for cancer immunotherapy.