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がんワクチン療法の開発

我々はこれまでに、がんペプチドワクチン療法の開発を通して、基礎研究からトランスレーショナルリサーチまでを実践し、多くの研究成果を報告してきました。特に、オリジナルのがん抗原であるglypican-3 (GPC3)およびHSP105については今後も開発を進めてまいります。

   研究内容1-1

研究内容1-2

  1. Tsuchiya N, Yoshikawa T, Fujinami N, Saito K, Mizuno S, Sawada Y, Endo I, Nakatsura T. Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma. OncoImmunology. in press 2017
  2. Suzuki S, Sakata J, Utsumi F, Sekiya R, Kajiyama H, Shibata K, Kikkawa F, Nakatsura T. Efficacy of Glypican-3-derived Peptide Vaccine Therapy on the Survival of Patients with Refractory Ovarian Clear Cell Carcinoma. OncoImmunology. 5;e1238542016
  3. Fujinami N, Yoshikawa T, Sawada Y, Shimomura M, Iwama T, Sugai S, Kitano S, Uemura Y, Nakatsura T. Enhancement of antitumor effect by peptide vaccine therapy in combination withanti-CD4antibody: Study in a murine model. Biochemistry and Biophysics Reports. 5;482-491,2016
  4. Sawada Y, Yoshikawa T, Ofuji K, Yoshimura M, Tsuchiya N, Takahashi M, Nobuoka D, Gotohda N, Takahashi S, Kato Y, Konishi M, Kinoshita T, Ikeda M, Nakachi K, Yamazaki N, Mizuno S, Takayama T, Yamao K, Uesaka K, Furuse J, Endo I, Nakatsura T. Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients. OncoImmunology. e1129483,2016
  5. Sawada Y, Yoshikawa T, Shimomura M, Iwama T, Endo I, Nakatsura T. Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes. Int. J. Oncol. 46:28-36,2015
  6. Sawada Y, Komori H, Tsunoda Y, Shimomura M, Takahashi M, Baba H, Ito M, Saito N, Kuwano H, Endo I, Nishimura Y, Nakatsura T. Identification of HLA-A2 or HLA-A24-restricted CTL epitopes for potential HSP105-targeted immunotherapy in colorectal cancer. Oncol. Rep. 31:1051-1058,2014
  7. Suzuki S, Shibata K, Kikkawa F, Nakatsura T. Significant Clinical Response of Progressive Recurrent Ovarian Clear Cell Carcinoma to Glypican-3-derived Peptide Vaccine Therapy: Two Case Reports. Hum Vacc Immunother. 10:338-343,2014
  8. Tada Y, Yoshikawa T, Shimomura M, Sawada Y, Sakai M,Shirakawa H, Nobuoka D and Nakatsura T. Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican‑3‑derived peptide. Int. J. Oncol. 43:1019-1026,2013
  9. Sawada Y, Yoshikawa T, Fujii S, Mitsunaga S, Nobuoka D, Mizuno S, Takahashi M, Yamauchi C, Endo I, Nakatsura T. Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination: An autopsy case.  Hum Vacc Immunother. 9:1228-1233,2013
  10. Nobuoka D, Yoshikawa T, Takahashi M, Iwama T, Horie K, Shimomura M, Suzuki S, Sakemura N, Nakatsugawa M, Sadamori H, Yagi T, Fujiwara T, Nakatsura T. Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement of antigen-specific cancer immunotherapy. Cancer Immunol Immun. 62:639-652,2013
  11. Sawada Y, Yoshikawa T, Nobuoka D, Shirakawa H, Kuronuma T, Motomura Y, Mizuno S, Ishii H, Nakachi K, Konishi M, Nakagori T, Takahashi S, Gotoda N, Takayama T, Yamao K, Uesaka K, Furuse J, Kinoshita T, Nakatsura T. Phase I trial of glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma : immunological evidence and potential for improving overall survival. Clin. Cancer Res. 18:3686-3692012
  12. Yoshikawa T, Nakatsugawa M, Suzuki S, Shirakawa H, Nobuoka D, Sakemura N, Motomura Y, Tanaka Y, Hayashi S, Nakatsura T. HLA-A2-restricted glypican-3 peptide-specific CTL clones induced by peptide vaccine show high avidity and antigen-specific killing activity against tumor cells. Cancer Sci. 102:918-22011
  13. Shirakawa H, Suzuki H, Shimomura M, Kojima M, Gotohda N, Takahashi S, Nakagohri T,  Konishi M, Kobayashi N, Kinoshita T, Nakatsura T. Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma. Cancer Sci. 100:1403-1402009
  14. Shirakawa H, Kuronuma T, Nishimura Y, Hasebe T, Nakano M, Gotohda N, Takahashi S, Nakagohri T, Konishi M, Kobayashi N, Kinoshita T, Nakatsura T. Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. Int. J. Oncol. 34:649-652009
  15. Motomura, Y., Ikuta, Y., Kuronuma, T., Komori, H., Ito, M., Tsuchihara, M., Tsunoda, Y., Shirakawa, H., Baba, H., Nishimura, Y., Kinoshita, T., and Nakatsura, T. HLA-A2 and -A2restricted Glypican-3-derived peptide vaccine induces specific CTLs: Preclinical study using mice. Int. J. Oncol. 32:985-992008
  16. Yokomine, K., Nakatsura, T., Senju, S., Nakagata, N., Minohara, M.,  Kira, JI., Motomura, Y., Kubo, T., Sasaki, Y., and Nishimura, Y.  Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+ mice. Cancer Sci. 98:1930-1932007
  17. Komori, H., Nakatsura, T., Senju, S., Yoshitake, Y., Motomura, Y., Ikuta, Y., Fukuma, D., Yokomine, K., Harao, M., Beppu, T., Matsui, M., Torigoe, T., Sato, N., Baba, H., and Nishimura, Y. Identification of HLA-Aor HLA–A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma. Clin. Cancer Res. 12689-2692006
  18. Yokomine, K., Nakatsura, T., Minohara, M., Kira, JI., Kubo, T., Sasaki, Y., and Nishimura, Y. Immunization with heat shock protein 105-pulsed dendritic cells leads to tumor rejection in mice. Biochem. Biophys. Res. Comm. 34269-272006
  19. Miyazaki, M.*, Nakatsura, T.*(*Equal contribution), Yokomine, K., Senju, S., Monji, M., Hosaka, S., Komori, H., Yoshitake, Y., Motomura, Y., Minohara, M., Kubo, T., Ishihara, K., Hatayama, T., Ogawa, M., and Nishimura, Y.  DNA vaccination of HSP1leads to tumor rejection of colorectal cancer and melanoma in mice through activation of both CDand CDT cells. Cancer Sci. 9695-702005
  20. Nakatsura, T., Komori, H., Kubo, T., Yoshitake, Y., Senju, S., Katagiri, T., Furukawa, Y., Oagawa, M., Nakamura, Y., and Nishimura, Y.  Mouse homologue of a novel human oncofetal antigen, Glypican-evokes T cell-mediated tumor rejection without autoimmune reactions in mice.  Clin. Cancer Res.  18630-8642004
  21. Kai, M., Nakatsura, T., Egami, H., Senju, S., Nishimura, Y., and Ogawa, M. Heat shock protein 1is overexpressed in a variety of human tumors.  Oncology Reports 11777-1782003
  22. Nakatsura, T., Yoshitake, Y., Senju, S., Monji, M., Komori, H., Motomura, Y., Hosaka, S., Beppu, T., Ishiko, T., Kamohara, H., Ashihara, H., Katagiri, T., Furukawa, Y., Fujiyama, S., Ogawa, M., Nakamura, Y., and Nishimura, Y. Glypican-overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker.   Biochem. Biophys. Res. Comm. 3016-22003
  23. Nakatsura, T., Senju, S., Yamada, K., Jyotsuka, T., Ogawa, M., and Nishimura, Y. Gene cloning of immunogenic antigens over-expressed in pancreatic cancer Biochem. Biophys. Res. Comm. 28936-942001