Cancer germline (CG; also known as cancer-testis) antigen genes are normally expressed in germ cells and trophoblast tissues and are aberrantly expressed in a variety of human malignancies. CG antigen genes have high clinical relevance as they encode a class of immunogenic and highly selective tumor. Official Full-Text Publication: Cancer testis antigens on ResearchGate, the professional network for scientists. Recently, we reported an association of a novel cancer testis (CT) antigen, sperm-associated antigen 9 (SPAG9) expression in breast cancer. Cancer Testis Antigens and Gametogenesis - Download as PDF File (.pdf), Text File (.txt) or read online. Hand-picked favorites from our editors. Breast cancer is a promising target for vaccination using cancer- testis antigens known to elicit immune responses . A limited number of reports have been published previously looking at breast cancer, but we have examined a larger panel of antigens than previously reported. CTAG1 has been reported to be expressed in 1. What the present report adds is that, in two separate series of tumours in the Southampton Tumour Bank, collected at different times, more than 8. Given that no individual antigen is expressed in all breast cancers, we were interested in examining the frequency of various combinations. In the first series of 4. Expression of cancer–testis antigens in endometrial carcinomas using a tissue microarray Dhananjay A Chitale 1, Achim A Jungbluth 2.CTAG1, CTp. 11 or SCP1. Seventy- three per cent of tumours in the second series expressed at least one of these three antigens. There would be undoubted attraction in a polyvalent vaccine with coverage of a larger proportion of tumours than is possible with vaccines directed against a single antigen. Polyvalent vaccines containing multiple melanoma CTL antigens are already in clinical development. T- cell responses, primarily CD8- mediated CTL responses, are believed to be the most important component of immune responses directed against CTAGs in human cancers. The initial descriptions of CTAGs were based on identification of antigens recognised by CTLs . An alternative strategy, SEREX, has been used subsequently to identify potential CTAGs; thus far, no CTL responses have been reported against some CTAGs identified in this way. The antigens CTp. SCP1 both fall into this group of CTAGs for which no CTL responses have yet been reported. We therefore examined patterns of expression of CTAGs known to induce CTL in humans. CTL responses have been identified against CTAG1, BAGE1 and MAGEA1. A vaccine directed against these three antigens would cover more than two- thirds of the tumours in each series of breast cancer examined in the present study. Construction of such a vaccine is entirely possible with currently available technology. We did not analyse the HLA status of the individuals from whom the tumour specimens were derived, but have no reason to believe this would be different from that of the UK population at large. CTAG1 is the most studied of the three antigens with identified responses, and peptides have been identified as being presented by HLA A2, HLA A3. HLA B7, HLA B3. 5, HLA B5. HLA Cw. 3 and HLA Cw. The frequency of these HLA alleles in the general population ranges between 5% and 4. MAGEA1. 0 peptides are known to be presented by HLA A2 (4. HLA B5. 3 (2%). BAGE1 has been studied least, and there is only the initial report of its presentation by HLA Cw. There is every reason to believe that other restriction elements (HLA alleles that present antigenic peptides) will be identified as further studies are undertaken. Analysis of the BAGE1 protein sequence using syfpeithi MHC epitope prediction software . Similarly, an even larger number of potential high- affinity epitope and restriction element pairs exists for MAGEA1. Clinical trials of immunisation against several CTAGs are underway. A search of the http: //Clinical. Trials. gov website . Although a number of trials of immunisation strategies in breast cancer are currently recruiting, we are not aware of any involving CTAGs. Our work, and that of others, would support inclusion of breast cancer patients in screening for entry into trials of vaccines against CTAGs. An interesting question for the future will be, if vaccination can induce demonstrable CTL responses against CTAGs expressed in breast cancer, whom should be offered such vaccination? Early trials looking to establish clinical benefit are likely to be performed in individuals with advanced disease, perhaps when few other treatment options remain. Breast cancer, almost uniquely, is a condition where active management of metastatic disease can include long periods of treatment with nonimmunosuppressive therapies (hormonal agents, herceptin). There is therefore also an opportunity for quite prolonged vaccination schedules without the concern that the concomitant use of cytotoxic therapy will disrupt the evolution of a normal immune response. The setting of minimal residual disease following surgery and adjuvant therapies, however, may be where vaccination could have its greatest impact, perhaps increasing the number of long- term cures. We examined whether there is an association between expression of CTAGs and markers of tumour aggressiveness. There was a trend towards higher numbers of CTAGs expressed with various features known to be associated with poorer prognosis. Similar findings were reported by Sugita and colleagues for CTAG1 . There was a trend towards expression of greater numbers of CTAGs with both increased risk of recurrence and breast- cancer- specific mortality. Park and colleagues . They found expression of at least one antigen of MAGEA1. It is not clear whether this represents a population difference (all their samples were derived from Korean patients), represents an increased sensitivity of the nested PCR technique they used, or represents chance. The same group subsequently demonstrated that they could detect PCR evidence of circulating tumour cells in a proportion of patients with breast cancer . Identification of circulating tumour cells may lead to earlier diagnosis of breast cancer, or to its recurrence. On the basis of the data presented here, the use of primers for CTAG1, MAGEA1. BAGE1 might increase the sensitivity of such a test.
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