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Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

Departments of ¹ Immunogenetics, ² Oral and Maxillofacial Surgery, and ³ Dermatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto; and ⁴ Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Saga University, Saga, Japan

ABSTRACT

Purpose: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/testis antigens that elicit both humoral and cellular immune responses in cancer patients.

Experimental Design and Results: We identified a novel gene designated KM-HN-1 the expression of which is testis-specific among normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402–positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24.

Conclusions: We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.

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