Application of cancer-testis antigens in immunotherapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide common malignancy with poor prognosis. Several studies have aimed at identification of appropriate biomarkers for early detection of this cancer. Cancer-testis antigens (CTAs) as a novel group of tumor-associated antigens have been demonstrated to be expressed in HCC samples as well as peripheral blood samples from these patients but not in the corresponding adjacent noncancerous samples. Such pattern of expression has provided them an opportunity to be used as immunotherapeutic targets. The detection of spontaneous immune responses against CTAs in HCC patients has prompted design of CTA-based immunotherapeutic protocols in these patients. The results of some clinical trials have been promising in a subset of patients.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: report of three cases from Iran.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also named as autoimmune polyglandular syndrome (APS) type 1, is a rare autosomal recessive disorder caused by mutations in autoimmune regulator (AIRE) gene. It is distinguished by an immune-mediated damage of endocrine tissues, chronic candidiasis, and ectodermal disorder. APECED has been shown to be frequent in some populations including Iranian Jews. Here we report three cases of APECED from two independent Iranian Muslim families. Addison's disease, hypoparathyroidismand mucocutaneous candidiasis were shared clinical manifestations in all patients. Mutational analyses have demonstrated a novel homozygous splice site mutation (c.1095+2T>A) in intron 9 and a previously identified homozygous nonsense mutation (c.415C>T) in exon 3 of patients respectively. Future studies are needed to evaluate the frequency of these variants in Iranian APECED patients which would facilitate genetic counseling as well as prenatal diagnosis.

Immunotherapy in Multiple Myeloma Using Cancer-Testis Antigens.

CONTEXT: Multiple myeloma (MM) is a B-cell malignancy characterized by monoclonal expansion of abnormal plasma cells in the bone marrow. It accounts for 10% of hematological malignancies. Although patients respond to a wide range of anticancer modalities, relapse occurs in a significant number of the cases. Immunotherapeutic approaches have been evolved to tackle this problem. Cancer-testis antigens CTAs as a group of tumor-associated antigens are appropriate targets for cancer immunotherapy as they have restricted expression pattern in normal tissues except for testis which is an immune-privileged site. Expression of these antigens has been assessed in different malignancies including MM. EVIDENCE ACQUISITION: We performed a computerized search of the MEDLINE/PubMed databases with key words: multiple myeloma, cancer-testis antigen, and cancer stem cell and immunotherapy. RESULTS: Several CTAs including NY-ESO-1, MAGE and GAGE family have been shown to be expressed in MM patients. Cellular and humoral immune responses against these antigens have been detected in MM patients. CONCLUSIONS: The frequent and high expression level of CTAs in MM patients shows that these antigens can be applied as cancer biomarkers as well as targets for immunotherapy in these patients.

Cancer-testis genes as candidates for immunotherapy in breast cancer.

Cancer-testis (CT) antigens are tumor-associated antigens attracting immunologists for their possible application in the immunotherapy of cancer. Several clinical trials have assessed their therapeutic potentials in cancer patients. Breast cancers, especially triple-negative cancers are among those with significant expression of CT genes. Identification of CT genes with high expression in cancer patients is the prerequisite for any immunotherapeutic approach. CT genes have gained attention not only for immunotherapy of cancer patients, but also for immunoprevention in high-risk individuals. Many CT genes have proved to be immunogenic in breast cancer patients suggesting the basis for the development of polyvalent vaccines.

Expression analysis of two cancer-testis genes, FBXO39 and TDRD4, in breast cancer tissues and cell lines.

Breast cancer accounts for one third of new cancer cases among women. The need for biomarkers for early detection is the stimulus to researchers to evaluate altered expression of genes in tumours. Cancer-testis (CT) genes are a group with limited expression in normal tissues except testis but up-regulation in a wide variety of cancers. We here evaluated expression of two CT genes named FBXO39 and TDRD4 in 32 invasive ductal carcinoma samples, 10 fibroadenomas and 6 normal breast tissue samples, in addition to two breast cancer cell lines, MCF-7 and MDA-MB-231, by the means of quantitative real time RT-PCR. FBXO39 showed significant up-regulation in invasive ductal carcinoma samples in comparison with normal samples. It also was expressed in both cell lines and after RHOXF1 gene knock down it was down-regulated in MCF-7 but up-regulated in the MDA-MB-231 cell line. TDRD4 was not expressed in the MCF-7 cell line and any of the tissue samples except testis. However, it was expressed in MDA-MB-231 and was up-regulated after RHOXF1 gene knock down. Our results show that FBXO39 but not TDRD4 can be used for cancer detection and if proved to be immunogenic, might be a putative candidate for breast cancer immunotherapy.