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Published on: February 8, 2016
Humoral immune responses to testis antigens in sera from patients with prostate cancer
Luke H Hoeppner1, Jason A Dubovsky, Edward J Dunphy
1Department of Medicine, University of Wisconsin, Madison, WI 53792, USA.
Abstract:
Tumor vaccines represent one type of molecularly targeted therapy being investigated for the treatment of prostate cancer. Although many prostate-specific proteins are being tested as target antigens for prostate cancer vaccines, most are not natural targets of an immune response in patients with cancer. Using sera from cancer patients, several research groups have identified a large family of immunologically recognized proteins whose expression is normally confined to immune-privileged testis tissue but which may be expressed in cancers of different histological origins. These proteins, so-called cancer-testis (CT) antigens, are appealing targets for immune-based therapies because they are essentially tumor-restricted antigens and there is less risk of preexisting immune tolerance. In addition, specifically targeting these proteins by means of vaccines should reduce the risk of potential autoimmune reactions to normal tissues. In the current study, we hypothesize that prostate CT antigens can be identified using a SEREX screening method with sera from patients with prostate cancer and probing with a human testis cDNA expression library. We have identified several potential prostate cancer antigens with predominantly testis-specific expression in normal tissues, including MAD-CT-1 (protamine 2) and MAD-CT-2. Each was independently identified from different subjects with prostate cancer. Antigens identified by these studies can be investigated further as potential prostate cancer tumor antigens.
Insights
Researchers identified novel prostate cancer antigens, MAD-CT-1 and MAD-CT-2, using a SEREX screening method. These cancer-testis (CT) antigens show promise for developing targeted prostate cancer vaccines with reduced autoimmune risks.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Prostate cancer treatment explores molecularly targeted therapies, including tumor vaccines.
- Most prostate-specific antigens are not natural targets for immune responses in cancer patients.
- Cancer-testis (CT) antigens, normally restricted to immune-privileged testis tissue, are expressed in various cancers and are promising targets for immune-based therapies due to tumor restriction and reduced immune tolerance.
Purpose of the Study:
- To identify potential prostate cancer antigens using the SEREX (Screening of Expressed sequence tags) method.
- To investigate cancer-testis (CT) antigens as targets for prostate cancer vaccines.
- To evaluate the feasibility of using sera from prostate cancer patients and a human testis cDNA expression library for antigen discovery.
Main Methods:
- Utilized the SEREX screening method.
- Employed sera from prostate cancer patients for screening.
- Probed a human testis cDNA expression library to identify target antigens.
Main Results:
- Identified several potential prostate cancer antigens with predominantly testis-specific expression in normal tissues.
- MAD-CT-1 (protamine 2) and MAD-CT-2 were identified as potential prostate cancer antigens.
- These antigens were independently identified from different prostate cancer patient samples.
Conclusions:
- Prostate cancer CT antigens can be identified using the SEREX screening method.
- MAD-CT-1 and MAD-CT-2 are potential candidates for further investigation as prostate cancer tumor antigens.
- Targeting these CT antigens may lead to effective prostate cancer vaccines with a lower risk of autoimmune reactions.
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