Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses
Mikio Monji,1,4 Tetsuya Nakatsura,1 Satoru Senju,1 Yoshihiro Yoshitake,1,2 Motohiro Sawatsubashi,4 Masanori Shinohara,2 Toshiro Kageshita,3 Tomomichi Ono,3 Akira Inokuchi,4 and Yasuharu Nishimura1
02/08/2011
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 testisspecific 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 KMHN- 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 KMHN- 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, KMHN- 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.