• Title, Summary, Keyword: Cancer-testis antigen

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Review of Cancer-Testis (CT) Genes (Cancer-testis (CT) 유전자의 고찰)

  • Kim, Mi-Hee;Song, Myung-Ha;Lee, Sang-Yull
    • Journal of Life Science
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    • v.21 no.6
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    • pp.912-922
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    • 2011
  • Cancer-testis (CT) antigens are immunogenic protein antigens with restricted expression in the testes and a wide range of human tumor types, eliciting both humoral and cellular immune responses in cancer patients. They are considered to be ideal targets for vaccine-based immunotherapy, and more than 100 CT antigens, including MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2 and NY-SAR-35 have been identified to date. The CT antigens were identified through various techniques and can be divided in those that are encoded on the X chromosome, the CT-X genes, and those that are not, the non-X-CT genes. CT genes are aberrantly activated and expressed in a proportion of various types of human cancers. The biological role of CT-X in both germ line tissues and tumors remains poorly understood. Cancer vaccine trials based on several CT antigens are currently ongoing. This paper reviews recent advances in and future trends of CT antigens for cancer immunotherapy.

A comprehensive Analysis of a Large Panel of Cancer/Testis (CT) Antigens in Korea Breast Cancer (한국 유방암 환자에서 cancer/testis antigen의 발현분석)

  • Bae, Jae-Ho;Kim, Min-Ju;Park, Hae-Rim;Song, Myung-Ha;Kim, Jee-Yeon;Lee, Chang-Hun;Kwak, Hi-Suk;Lee, Sang-Yull
    • Journal of Life Science
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    • v.19 no.7
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    • pp.886-891
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    • 2009
  • Cancer/testis (CT) antigens are immunogenic in cancer patients, exhibit highly tissue-restricted expression, and are considered promising target molecules for cancer vaccines. We investigated the expression of 13 CT genes in 29 Korean patients with primary breast carcinoma. The most frequently expressed CT genes were MAGE-3 (66%) and MAGE-1 (57%), followed by LAGE-1 (55%), NY-SAR-35 (49%), MAGE-4 (41%), NY-ESO-1 (38%), CT-7 (24%) and SSX-4 (24%), whereas SSX-1, SSX-2, MAGE-10 and NY-TLU-57 were found to be expressed significantly less often (3-7%) and SCP-l not all. Expression of at least one antigen was observed in 28 breast cancer samples. Immunohistochemistry was performed for NY-ESO-l and MAGE-3 protein expression in breast tumor samples. NY-ESO-l and MAGE-3 proteins were expressed in 11 of 29 (38%) and 12 of 29 (41 %) breast tumors. Our results suggest that CT antigens may be potential candidates for polyvalent immunotherapy in Korean breast cancer patients.

Role of CAGE, a Novel Cancer/Testis Antigen, in Various Cellular Processes, Including Tumorigenesis, Cytolytic T Lymphocyte Induction, and Cell Motility

  • Kim, Young-Mi;Jeoung, Doo-Il
    • Journal of Microbiology and Biotechnology
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    • v.18 no.3
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    • pp.600-610
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    • 2008
  • A cancer-associated antigen gene (CAGE) was identified by serological analysis of a recombinant cDNA expression library (SEREX). The gene was identified by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera from patients with gastric cancer. CAGE was found to contain a D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. The CAGE gene is widely expressed in various cancer tissues and cancer cell lines. Demethylation plays a role in the activation of CAGE in certain cancer cell lines where the gene is not expressed. The functional roles of CAGE in tumorigenesis, the molecular mechanisms of CAGE expression, and cell motility are also discussed.

Identification of Tumor Antigens in Lung Cancer Patient by SEREX (폐암 환자에서 면역항원유전자의 혈청학적 동정)

  • Min, Young-Ki;Ha, Jin-Mok;Son, Young-Ok;Park, Hae-Rim;Lee, Min-Ki;Park, Yeoung-Min;Kim, Cheol-Min;Lee, Sang-Yull
    • Journal of Life Science
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    • v.17 no.8
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    • pp.1082-1089
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    • 2007
  • Serological anlysis of recombinant cDNA expression libraries (SEREX) has led to identification of several categories of new antigens recognized by the immune system of cancer patients, which are referred to as the cancer immunome. We analyzed normal testis cDNA expression libraries with serumobtained from non-small lung cancer patient and isolated 40 distinct antigen designated KP-LuT-1 through KP-LuT-40. Among these antigens 20 antigens were previously identified by SEREX analysis of other tumor types, and 20 out of 40 antigens (50%) did not match entries in Cancer Immunome Database and were considered newly identified antigens. Sequencing analysis showed that the anti-gens comprised 26 functional known proteins and 14 noble/uncharacterized gene products. Of these, the hypothetical protein KP-LuT-6 was shown tissue-restricted. RT-PCR showed it to be expressed strongly only in normal testis. In addition to normal tissues-restricted expression, KP-LuT-6 mRNA was detected in lung tumor samples(3/l0), stomach tumor samples(3/l0), and breast tumor samples(l/5), whereas not detected in colon tumor samples(O/I2). These data suggest that KP-LuT-6 is a cancer/testis (CT)-like antigen as a potential target for cancer immunotherapies.

Identification and characterization of a novel cancer/testis antigen gene

  • Cho , Bom-Soo;Lee, Dae-Yeon;Lim , Yoon;Park, Sae-Young;Lee, Ho-Soon;Kim, Woo-Ho;Yang, Han-Kwang;Bang, Yung-Jue;Jeoung , Doo-Il
    • Proceedings of the PSK Conference
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    • pp.326.1-326
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    • 2002
  • We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. (omitted)

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Are So-Called Cancer-Testis Genes Expressed Only in Testis?

  • Ghafouri-Fard, Soudeh;Rezazadeh, Fatemeh;Zare-Abdollahi, Davood;Omrani, Mir Davood;Movafagh, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7703-7705
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    • 2014
  • Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.

Expression of Cancer-Testis Antigens in Stem Cells: Is it a Potential Drawback or an Advantage in Cancer Immunotherapy

  • Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.3079-3081
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    • 2015
  • Cancer-testis antigens (CTAs) are a group of tumor associated antigens with a restricted expression pattern in normal gametogenic tissues but expression in a broad range of malignancies. Their expression pattern has made them potential targets for immunotherapy. However, expression of some of these antigens has been demonstrated in normal stem cells as well as cancer stem cells (CSCs). As CSCs have been shown to be sources of metastasis and tumor recurrence, novel therapies are being focused on their eradication. On the other hand, CTA expression in normal stem cells raises the possibility that CTA based immunotherapies cause side effects in normal tissues.

Expression of Cancer-Testis Antigens in Pediatric Cancers

  • Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5149-5152
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    • 2015
  • Cancer-testis antigens (CTAs) are a group of tumor-associated antigens with more than 140 members whose expression has been shown to be limited to gametogenic tissues and placenta among normal tissues. However, malignant tissues of different origins have shown aberrant and elevated expression of these antigens. Such a pattern of expression endows beneficial properties for use as cancer biomarkers as well as immunotherapeutic targets as a result of the immune-privileged status of the testes. CTAs have been shown to be expressed in pediatric brain tumors, different types of sarcomas, leukemias, and lymphomas as well as neuroblastomas. Although data regarding their expression pattern in childhood tumors are not as comprehensive as for adult tumors, it is supposed that CTA-based immunotherapeutic approaches can also be used for pediatric cancers. However, there are limited data about the objective clinical responses following immunotherapy in such patients. Here we try to review the available information.

The cancer/testis antigen CAGE induces MMP-2 through the activation of NF-κB and AP-1

  • Kim, Young-Mi;Jeoung, Doo-Il
    • BMB Reports
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    • v.42 no.11
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    • pp.758-763
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    • 2009
  • Cancer-associated antigen (CAGE) induces the expression of matrix metalloproteinase-2 (MMP-2) by activating Akt, which in turn interacts with inhibitory kappa kinase $\beta$ ($I{\kappa}K{\beta}$) to activate nuclear factor ${\kappa}B$ (NF-${\kappa}B$). Akt and p38 mitogen activated protein kinase (p38 MAPK) are necessary for CAGE-mediated induction of the AP-1 subunit JunB, whereas extracellular regulated kinase (ERK) is necessary for the induction of fos-related antigen-1 (Fra-1). Induction of MMP-2 by CAGE requires activator of protein-1 (AP-1) to be bound. Specific binding of JunB to MMP-2 promoter sequences was shown by chromatin immunoprecipitation (ChIP) analysis.