One focus in the field of tumor immunology is the identification of cancer-specific antigens that might be exploited as therapeutic targets or as immunologic diagnostic markers. Cancer-testis antigens (CTAs) are of particular interest as potential target antigens given that their expression is typically restricted to germ cells among normal tissues, but aberrantly expressed in multiple tumor types. In the current report, we sought to evaluate serum antibody immune responses to a defined panel of CTA from multiple antigen families to identify potential tumor-specific antigens that could potentially serve as candidate target antigens for immunotherapy or diagnostic purposes. This was conducted by screening sera from male patients with metastatic melanoma (n=44) and volunteer blood donors (n=50) against a panel of lambda phage-encoded CTA. We found that IgG antibody responses occurred in 39% of patients with melanoma to at least one of these antigens compared with 4% of controls (P<0.001). We found antibody responses to one antigen, MAD-CT-2, occurred in 27% of patients compared with 0/50 controls (P<0.0001). These findings, along with the demonstration that MAD-CT-2 is expressed in melanoma cell lines, identified MAD-CT-2 as a novel melanoma CTA.
"bacterial lawns in OmniTray plates using a Biomek FX liquid handling robot. These individual antigens included 29 cancer-testis antigens , 40 proteins identified in patients with chronic prostatitis , and 57 antigens identified in individual patients, some of whom were treated with androgen deprivation or other immunomodulatory therapies   . A listing of antigens and their GenBank Accession numbers is included in Supple- mental "
[Show abstract][Hide abstract] ABSTRACT: We previously demonstrated that IgG responses to a panel of 126 prostate tissue-associated antigens are common in patients with prostate cancer. In the current report we questioned whether changes in IgG responses to this panel might be used as a measure of immune response, and potentially antigen spread, following prostate cancer-directed immune-active therapies. Sera were obtained from prostate cancer patients prior to and three months following treatment with androgen deprivation therapy (n = 34), a poxviral vaccine (n = 31), and a DNA vaccine (n = 21). Changes in IgG responses to individual antigens were identified by phage immunoblot. Patterns of IgG recognition following three months of treatment were evaluated using a machine-learned Bayesian Belief Network (ML-BBN). We found that different antigens were recognized following androgen deprivation compared with vaccine therapies. While the number of clinical responders was low in the vaccine-treated populations, we demonstrate that ML-BBN can be used to develop potentially predictive models.
BioMed Research International 01/2011; 2011(1110-7243):454861. DOI:10.1155/2011/454861 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Almost 100 years ago, Ehrlich and coworkers observed the presence of infiltrates of mononuclear cells around or inside tumor
lesions . This finding led them to propose that tumors could be recognized and inhibited by the ‘magic bullets’ of the
immune system. At the end of the 19th century, studies were initiated that aimed at actively immunizing cancer patients against
their own cancerous tissue. During the subsequent decades, cancer patients were nonspecifically immune-stimulated with relatively
crude leukocyte extracts such as transfer factor, immune- RNA, bacterial extracts such as bacillus Calmette- Guerain, Coley’s
toxin or levamisole. These studies were initiated in spite of the fact that little was known about the various components
of the immune system that could react against cancer, and even less was known about the structures on cancer cells that can
be recognized by the immune system.
[Show abstract][Hide abstract] ABSTRACT: Active immunotherapies are one approach being developed as novel treatments for prostate cancer. Critical to the success of these therapies is the identification of appropriate target antigens. We have been seeking to identify immunologically recognized proteins, cancer-testis antigens (CTA) in particular, in patients with prostate cancer that would be rational target antigens.
Using a previously reported panel of 29 different CTA, we used sera from 98 patients with prostate cancer and 50 healthy male blood donor controls to detect CTA-specific IgG. We then further evaluated the expression of one antigen, SSX-2, in prostate cancer cell lines and tissues.
We identified IgG specific for NY-ESO-1, LAGE-1, NFX-2, and SSX-2 in at least 1/98 individuals with prostate cancer. We demonstrated that SSX-2 is a prostate CTA, and its expression is associated with metastatic prostate cancer. In addition, we report that the treatment of at least two human prostate cancer cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced the expression of SSX-2. In contrast, treatment of a normal prostate epithelial cell line (RWPE-1) with 5-aza-2'-deoxycytidine did not induce SSX-2 expression.
Our findings suggest that SSX-2 could be further pursued as an immunotherapeutic target in prostate cancer, and that treatment with 5-aza-2'-deoxycytidine could be exploited to modulate antigen expression in combination with immunotherapeutic approaches.
The Prostate 12/2007; 67(16):1781-90. DOI:10.1002/pros.20665 · 3.57 Impact Factor
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