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Identification of CCDC62-2 as a novel cancer/testis antigen and its immunogenicity
Shohei Domae1, Yoichi Nakamura, Yurika Nakamura
1Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, Japan.
Abstract:
Cancer/testis (CT) antigens are expressed in normal germ line tissues and various cancers. They are considered promising target molecules for immunotherapy for patients with various cancers. To identify CT antigens, we performed serological identification of antigens by recombinant expression cloning. The humoral immune response of cancer patients against a newly defined antigen was analyzed. A testicular cDNA library was immunoscreened with serum obtained from a gastric adenocarcinoma patient whose primary cancer had regressed once and most liver metastases had disappeared transiently. We isolated 55 positive cDNA clones comprising 23 different genes. They included 4 genes with testis-specific expression profiles in the Unigene database, including coiled-coil domain containing 62 (CCDC62). RT-PCR analysis showed that the expression of 2 splice variants of CCDC62 was restricted to the testis in normal adult tissues. In malignant tissues, CCDC62 variant 2 (CCDC62-2) was aberrantly expressed in a variety of cancers, including stomach cancer. A serological survey of 191 cancer patients with a range of different cancers by ELISA revealed antibodies to CCDC62-2 in 13 patients, including stomach cancer. None of the 41 healthy donor serum samples were reactive in the same test. The serum reaction against CCDC62-2 was confirmed by western blot. CCDC62-2 is a CT antigen that is immunogenic in cancer patients.
Insights
Cancer/testis antigens are promising for cancer immunotherapy. Researchers identified CCDC62-2 as a novel cancer/testis antigen expressed in various cancers and immunogenic in patients, suggesting its potential as an immunotherapy target.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cancer/testis (CT) antigens are recognized as potential targets for cancer immunotherapy due to their restricted expression in normal tissues and presence in various malignancies.
- Identifying novel CT antigens is crucial for developing effective immunotherapeutic strategies against cancer.
Observation:
- A testicular cDNA library was screened using serum from a gastric adenocarcinoma patient, leading to the identification of 55 positive cDNA clones representing 23 genes.
- Among these, coiled-coil domain containing 62 (CCDC62) was identified, with two splice variants showing testis-specific expression in normal tissues.
- CCDC62 variant 2 (CCDC62-2) exhibited aberrant expression in multiple cancer types, including stomach cancer.
Findings:
- CCDC62-2 was found to be aberrantly expressed in various malignant tissues, notably stomach cancer.
- Serological analysis revealed antibodies against CCDC62-2 in 13 out of 191 cancer patients, but not in healthy donors.
- Western blot analysis confirmed the specificity of the serum reaction against CCDC62-2.
Implications:
- CCDC62-2 is confirmed as a novel cancer/testis antigen.
- The immunogenicity of CCDC62-2 in cancer patients highlights its potential as a target for developing cancer immunotherapies.
- Further research into CCDC62-2 could lead to new diagnostic and therapeutic approaches for various cancers.
