Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses

Mikio Monji, Tetsuya Nakatsura, Satoru Senju, Yoshihiro Yoshitake, Motohiro Sawatsubashi, Masanori Shinohara, Toshiro Kageshita, Tomomichi Ono, Akira Inokuchi, Yasuharu Nishimura

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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.

Original languageEnglish
Pages (from-to)6047-6057
Number of pages11
JournalClinical Cancer Research
Volume10
Issue number18 I
DOIs
Publication statusPublished - Sep 15 2004

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Testicular Neoplasms
Humoral Immunity
Cellular Immunity
Antigens
Neoplasms
HN Protein
HLA Antigens
Tissue Donors
Cell Line
Testis
Immunoglobulin G
Leucine Zippers
Antibodies
Esophageal Neoplasms
Gene Library
Mitosis
Immunotherapy
Fluorescent Antibody Technique
Proteins
Research Design

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Monji, M., Nakatsura, T., Senju, S., Yoshitake, Y., Sawatsubashi, M., Shinohara, M., ... Nishimura, Y. (2004). Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses. Clinical Cancer Research, 10(18 I), 6047-6057. https://doi.org/10.1158/1078-0432.CCR-04-0475

Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses. / Monji, Mikio; Nakatsura, Tetsuya; Senju, Satoru; Yoshitake, Yoshihiro; Sawatsubashi, Motohiro; Shinohara, Masanori; Kageshita, Toshiro; Ono, Tomomichi; Inokuchi, Akira; Nishimura, Yasuharu.

In: Clinical Cancer Research, Vol. 10, No. 18 I, 15.09.2004, p. 6047-6057.

Research output: Contribution to journalArticle

Monji, M, Nakatsura, T, Senju, S, Yoshitake, Y, Sawatsubashi, M, Shinohara, M, Kageshita, T, Ono, T, Inokuchi, A & Nishimura, Y 2004, 'Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses', Clinical Cancer Research, vol. 10, no. 18 I, pp. 6047-6057. https://doi.org/10.1158/1078-0432.CCR-04-0475
Monji, Mikio ; Nakatsura, Tetsuya ; Senju, Satoru ; Yoshitake, Yoshihiro ; Sawatsubashi, Motohiro ; Shinohara, Masanori ; Kageshita, Toshiro ; Ono, Tomomichi ; Inokuchi, Akira ; Nishimura, Yasuharu. / Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 18 I. pp. 6047-6057.
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AU - Nakatsura, Tetsuya

AU - Senju, Satoru

AU - Yoshitake, Yoshihiro

AU - Sawatsubashi, Motohiro

AU - Shinohara, Masanori

AU - Kageshita, Toshiro

AU - Ono, Tomomichi

AU - Inokuchi, Akira

AU - Nishimura, Yasuharu

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N2 - 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.

AB - 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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