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Frequent Immune Responses to a Cancer/Testis Antigen, CAGE, in Patients with Microsatellite instability–Positive Endometrial Cancer

Authors' Affiliations: ¹ Division of Cellular Signaling, Institute for Advanced Medical Research, ² Department of Obstetrics and Gynecology, School of Medicine, Keio University, ³ Department of Advanced Medical Science, Institute of Medical Science, University of Tokyo, Tokyo, and ⁴ Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan

Requests for reprints: Yutaka Kawakami, Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan. Phone: 81-3-5363-3778; Fax: 81-3-5362-9259; E-mail: yutakawa{at}sc.itc.keio.ac.jp.

Purpose: Identification of cancer/testis antigens useful for diagnosis or immunotherapy of cancers was attempted by cDNA expression cloning with patients' sera (SEREX).

Experimental Design: cDNA expression libraries made from testis or endometrial cancer cell lines were screened using sera from patients with endometrial cancer or melanoma patients immunized with dendritic cells pulsed with autologous tum or lysates. Tissue-specific expression by RT-PCR and immunogenicity by Western blotting of the bacterial recombinant antigen with sera from cancer patients were evaluated.

Results: A cancer/testis antigen, CAGE, was isolated by two independently performed SEREX. CAGE was expressed in various cancer cell lines including endometrial cancer, colon cancer, and melanoma in 7 of 10 endometrial cancer tissues and in 1 of 3 atypical endometrial hyperplasia, but not in normal tissues including the endometrium and testis. The protein expression on cancer cells was confirmed by Western blot analysis with the recombinant CAGE protein, anti-CAGE IgG antibody was detected in sera from 5 of 45 endometrial cancer, 2 of 24 melanoma, and 2 of 33 colon cancer patients, but not in sera from healthy individuals. By ELISA analysis, anti-CAGE antibody was detected in 12 of 45 endometrial cancer, 2 of 20 melanoma, and 4 of 33 colon cancer patients. Intriguingly, anti-CAGE antibody was highly positive in 7 of the 13 (53.8%) microsatellite instability (MSI)-H patients with endometrial cancer, but negative in 20 non–MSI-H patients (P = 0.001).

Conclusion: CAGE may be useful for immunotherapy and diagnosis of various cancers particularly MSI-positive endometrial cancer.

Key Words: SEREX • tumor antigen • melanoma • immunotherapy • immunodiagnosis

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