Development of Novel Cancer Immunotherapy Targeting Mutated Genes: Identification of Antigen Epitopes Derived from the Mutated KRAS and EGFR Genes.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591913
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kurume University
• Principal Investigator: SASADA Tetsuro 久留米大学, 医学部, 准教授 (70293967)
• Project Period (FY): 2011 – 2013
• Keywords: 免疫療法 / 突然変異遺伝子 / T細胞エピトープ / ペプチドワクチン / 上皮成長因子受容体（EGFR) / KRAS

Research Abstract

Personalized cancer treatments targeting oncogenic mutated genes are currently developing. Since mutated genes are recognized as foreign by the host immune system, they might be an appropriate target for cancer immunotherapy. In the current study, we have identified two antigen epitopes derived from the epidermal growth factor receptor (EGFR) T790M mutation, which is known to cause resistance to gefitinib in non-small cell lung cancer, and one antigen epitope derived from the KRAS (G12V) mutation, which is frequently detected in colorectal cancer. Our results could provide a novel immunotherapeutic approach for treatment against refractory advanced cancer patients with these mutations, and might lead to development of "personalized immunotherapy targeting mutated genes".

Research Products

• [Journal Article] Feasibility study of personalized peptide vaccination for recurrent ovarian cancer patients (2014)
  • Author(s): Kawano K, Tsuda N, Matsueda S, Sasada T, Watanabe N, Ushijima K, Yamaguchi T, Yokomine M, Itoh K, Yamada A, Kamura T.
  • Journal Title: Immunopharmacol Immunotoxicol Volume: (in press)
• [Journal Article] Personalized peptide vaccine for treatment of advanced cancer (2014)
  • Author(s): Sasada T, Yamada A, Noguchi M, Itoh K.
  • Journal Title: Curr Med Chem. Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Humoral Immune Responses to EGFR-derived Peptides Predict Progression-free and Overall Survival of Non-small Cell Lung Cancer Patients Receiving Gefitinib (2014)
  • Author(s): Azuma K, Komatsu N, Hattori S, Matsueda S, Kawahara A, Sasada T, Itoh K, Hoshino T.
  • Journal Title: PLoS One Volume: 9(1) Pages: e86667
  • DOI: 10.1371/journal.pone.0086667
  • Peer Reviewed
• [Journal Article] EGFR T790M Mutation as a Possible Target for Immunotherapy; Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the EGFR T790M Mutation (2013)
  • Author(s): Yamada T, Azuma K, Muta E, Kim J, Sugawara S, Zhang GL, Matsueda S, Kasama-Kawaguchi Y, Yamashita Y, Yamashita T, Nishio K, Itoh K, Hoshino T, Sasada T.
  • Journal Title: PLoS One Volume: 8(11) Pages: e78389
  • DOI: 10.1371/journal.pone.0078389
  • Peer Reviewed
• [Journal Article] Personalized peptide vaccination : a new approach for advanced cancer as therapeutic cancer vaccine (2013)
  • Author(s): Noguchi M, Sasada T, Itoh K.
  • Journal Title: Cancer Immunol Immunother Volume: 62 Pages: 919-29
  • Peer Reviewed
• [Journal Article] A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients : Prolongation of prostate-specific antigen doubling time (2013)
  • Author(s): Noguchi M, Moriya F, Suekane S, Ohnishi R, Matsueda S, Sasada T, Yamada A and Itoh K.
  • Journal Title: BMC Cancer Volume: 13 Pages: 613
  • DOI: 10.1186/1471-2407-13-613
  • Peer Reviewed
• [Journal Article] Current status of immunotherapy for the treatment of biliary tract cancer (2013)
  • Author(s): Takahashi R, Yoshitomi M, Yutani S, Shirahama T, Noguchi M, Yamada A, Itoh K, Sasada T.
  • Journal Title: Hum Vaccin Immunother Volume: 9(5) Pages: 1069-1072
  • Peer Reviewed
• [Journal Article] A phase II study of a personalized peptide vaccination for chemotherapy-resistant advanced pancreatic cancer patients (2013)
  • Author(s): Yutani S, Komatsu N, Yoshitomi M, Matsueda S, Yonemoto K, Mine T, Noguchi M, Ishihara Y, Yamada A, Itoh K, Sasada T.
  • Journal Title: Oncol Rep. Volume: 30(3) Pages: 1094-100
  • Peer Reviewed
• [Journal Article] Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients (2013)
  • Author(s): Takahashi R, Ishibashi Y, Hiraoka K, Matsueda S, Kawano K, Kawahara A, Kage M, Ohshima K, Yamanaka R, Shichijo S, Shirouzu K, Itoh K, Sasada T.
  • Journal Title: Cancer Sci. Volume: 104(10) Pages: 1285-94
  • Peer Reviewed
• [Journal Article] Juzentaihoto Failed to Augment Antigen-Specific Immunity but Prevented Deterioration of Patients' Conditions in Advanced Pancreatic Cancer under Personalized Peptide Vaccine (2013)
  • Author(s): Yutani S, Komatsu N, Matsueda S, Yoshitomi M, Shirahama T, Yamada A, Itoh K, Sasada T.
  • Journal Title: Evid-Based Compl Alt. Volume: Article ID 981717
  • DOI: 10.1155/2013/981717
  • Peer Reviewed
• [Journal Article] The next generation of peptide vaccines for advanced cancer (2013)
  • Author(s): Yamada A, Sasada T, Noguchi M, Itoh K .
  • Journal Title: Cancer Sci. Volume: 104(1) Pages: 15-21
  • Peer Reviewed
• [Journal Article] Gene expression profiles in peripheral blood as a biomarker in cancer patients receiving peptide vaccination (2012)
  • Author(s): Komatsu K, Matsueda S, Tashiro K, Ioji T, Shichijo S, Noguchi M, Yamada A, Doi A, Suekane S, Moriya F, Matsuoka K, Kuhara S, Itoh K, Sasada T.
  • Journal Title: Cancer Volume: 118(12) Pages: 3208-21
  • Peer Reviewed
• [Journal Article] Personalized peptide vaccination in patients with refractory non-small cell lung cancer (2012)
  • Author(s): Yoshiyama K, Terazaki Y, Satoko Matsueda S, Shichijo S, Noguchi M, Yamada A, Mine T, Ioji T, Itoh K, Shirouzu K, Sasada T, Takamori S.
  • Journal Title: Int J Oncol Volume: 40 Pages: 1492-500
  • Peer Reviewed
• [Journal Article] Personalized peptide vaccination for advanced biliary tract cancer : IL-6, nutritional status, and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis (2012)
  • Author(s): Yoshitomi M, Yutani S, Matsueda S, Ioji T, Komatsu N, Shichijo S, Yamada A, Itoh K, Sasada T, Kinoshita H.
  • Journal Title: Exp Ther Med. Volume: 3(3) Pages: 463-469
  • Peer Reviewed
• [Journal Article] Phase II study of personalized peptide vaccination in patients with castration-resistant prostate cancer evaluating progression status with or without prior docetaxel-based chemotherapy (2012)
  • Author(s): Noguchi M, Moriya F, Suekane S, Arai G, Yoshihara K, Ioji T, Matsueda S, Sasada T, Yamada A, Itoh K.
  • Journal Title: Prostate Volume: 72(8) Pages: 834-45
  • Peer Reviewed
• [Journal Article] Immunological Evaluation of Personalized Peptide Vaccination in Refractory Small Cell Lung Cancer (2012)
  • Author(s): Terazaki Y, Yoshiyama K, Matsueda S, Watanabe N, Kawahara A, Naito Y, Suekane S, Komatsu N, Ioji T, Yamada A, Mine T, Terasaki M, Itoh K, Takamori S, Sasada T.
  • Journal Title: Cancer Sci. Volume: 103(4) Pages: 638-44
  • Peer Reviewed
• [Journal Article] Personalized peptide vaccination : a novel immunotherapeutic approach for advanced cancer (2012)
  • Author(s): Sasada T, Noguchi M, Yamada A, Itoh K.
  • Journal Title: Hum Vaccin Immunother Volume: 8(9) Pages: 1309-1313
  • Peer Reviewed
• [Journal Article] Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination (2011)
  • Author(s): Noguchi M, Mine T, Komatsu N, Suekane S, Moriya F, Matsuoka K, Yutani Y, Shichijo S, Yamada A, Toh U, Kawano K, Azuma K, Uemura H, Okuno K, Matsumoto K, Yanagimoto H, Yamanaka R, Oka M, Todo S, Sasada T, Itoh K.
  • Journal Title: Cancer Biol Ther. Volume: 10 Pages: 1266-79
  • Peer Reviewed
• [Presentation] EGFR T790M mutation as a novel target for immunotherapy against EGFR-TKI-resistant non-small cell lung cancer (2013)
  • Author(s): Sasada T, et al.
  • Organizer: 28th Annual Meeting of Society for Immunotherapy of Cancer (SITC)
  • Place of Presentation: National Harbor, MD, USA
  • Year and Date: 2013-11-08
• [Presentation] EGFR T790M-derived T Cell Epitopes as a Target for Immunotherapy against EGFR-TKI-resistant Non-Small Cell Lung Cancer (2013)
  • Author(s): Yamada T, Sasada T, et al.
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2013-10-05
• [Presentation] EGFR T790M Mutation as a Novel Target for Immunotherapy against EGFR-TKI-resistant Non-Small Cell Lung Cancer (2013)
  • Author(s): Yamada T, Sasada T, et al.
  • Organizer: 第17回日本がん免疫学会総会
  • Place of Presentation: 宇部市
  • Year and Date: 2013-07-05
• [Book] Personalized peptide vaccine as a novel immunotherapy against advanced cancer, Molecular Vaccines - From Prophylaxis to Therapy (2013)
  • Author(s): Komatsu N, Matsueda S, Noguchi M, Yamada A, Itoh K, Sasada T.
  • Total Pages: 361-369
  • Publisher: In Giese Med
• [Patent(Industrial Property Rights)] 上皮成長因子受容体のT790M点突然変異配列に由来する抗原ペプチド (2013)
  • Inventor(s): 笹田哲朗、中面哲也、大藤和也
  • Industrial Property Rights Holder: 久留米大学、国立がんセンター
  • Industrial Property Rights Type: 国際特許
  • Industrial Property Number: PCT/JP2013/071499
  • Filing Date: 2013-08-08
  • Overseas
• [Patent(Industrial Property Rights)] 上皮成長因子受容体のT790M点突然変異配列に由来する抗原ペプチド (2012)
  • Inventor(s): 笹田哲朗
  • Industrial Property Rights Holder: 久留米大学
  • Industrial Property Rights Type: 国際特許
  • Industrial Property Number: 特願2012-177631
  • Filing Date: 2012-08-10
  • Overseas