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.
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 cancerpatients. 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 cancerpatients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402-positive healthy donors and cancerpatients, 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 cancerpatients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.
Authors: Junhao Wen; Cynthia H Y Fu; Duygu Tosun; Yogasudha Veturi; Zhijian Yang; Ahmed Abdulkadir; Elizabeth Mamourian; Dhivya Srinivasan; Ioanna Skampardoni; Ashish Singh; Hema Nawani; Jingxuan Bao; Guray Erus; Haochang Shou; Mohamad Habes; Jimit Doshi; Erdem Varol; R Scott Mackin; Aristeidis Sotiras; Yong Fan; Andrew J Saykin; Yvette I Sheline; Li Shen; Marylyn D Ritchie; David A Wolk; Marilyn Albert; Susan M Resnick; Christos Davatzikos Journal: JAMA Psychiatry Date: 2022-05-01 Impact factor: 25.911