Development of immunotherapy for lung adenocarcinoma using XAGE1 antigen and serum antibody as biomarkers

• Project/Area Number: 15K09235
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: Oka Mikio 川崎医科大学, 医学部, 教授 (40223995)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺がん / がん精巣抗原 / がん免疫 / がん免疫療法 / 予後因子 / 免疫チェックポイント / 抗体療法 / 個別化医療 / がん免疫応答 / バイオマーカー / 腫瘍免疫 / がん抗原 / 肺腺がん / 免疫モニタリング

Outline of Final Research Achievements

Firstly, relationship between immune-related molecules and prognosis was investigated in 120 lung adenocarcinoma tissues, resulted in independent poor prognostic factors of XAGE1 expression and negative T-cell infiltration. Then, the formula predicting their prognosis was created by cluster classification using tumor PD-L1, galectin-9, and XAGE1 antigen expression, and T-cell infiltration, and it almost accurately predicted their prognosis.
Secondly, we found that XAGE1 antigen was expressed in approximately 50% of lung adenocarcinomas and that it’s antibody was detected in almost half of those with XAGE1 antigen. As one reason for negative XAGE1antibody in lung adenocarcinomas with XAGE1 antigen, regulatory T-cell and B-cell infiltrate into tumor site.
Thirdly, we found a bio marker predicting response to immunotherapy in non-small cell lung cancer and applied the patent (#2017-094986) in Japan, however; the biomarker cannot be open here because of submitting its paper.

Research Products

• [Journal Article] NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC (2017)
  • Author(s): Takeoka T, Nagase H, Kurose K, Ohue Y, Yamasaki M, Takiguchi S, Sato E, Isobe M, Kanazawa T, Matsumoto M, Iwahori K, Kawashima A, Morimoto-Okazawa A, Nishikawa H, Oka M, Pan L, Venhaus R, Nakayama E, Mori M, Doki Y, Wada H.
  • Journal Title: J Immunother Volume: epub Issue: 4 Pages: 140-147
  • DOI: 10.1097/cji.0000000000000162
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Possible role of IL-25 in eosinophilic lung inflammation in patients with chronic eosinophilic pneumonia. (2017)
  • Author(s): Katoh S, Ikeda M, Matsumoto N, Shimizu H, Abe M, Ohue Y, Mouri K, Nakazato M, Oka M.
  • Journal Title: Lung Volume: 195 Issue: 6 Pages: 707-712
  • DOI: 10.1007/s00408-017-0048-8
  • Peer Reviewed / Open Access
• [Journal Article] Biomarkers for differentiation of patients with asthma and chronic obstractive pulmonary disease. (2017)
  • Author(s): Katoh S, Ikeda M, Shirai R, Abe M, Ohue Y, Kobashi Y, Oka M.
  • Journal Title: Journal of Asthma Volume: 16 Issue: 10 Pages: 1-7
  • DOI: 10.1080/02770903.2017.1391281
  • Peer Reviewed
• [Journal Article] Beneficial effects of Galectin-9 on allergen-specific sublingual immunotherapy in a <i>Dermatophagoides farinae</i>-induced mouse model of chronic asthma (2017)
  • Author(s): Ikeda M, Katoh S, Shimizu H, Oka M.
  • Journal Title: Allergology International Volume: 66 Issue: 3 Pages: 432-439
  • DOI: 10.1016/j.alit.2016.10.007
  • NAID: 130005858794
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Survival of lung adenocarcinoma patients predicted from expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a) on tumor cells and tumor-infiltrating T cells. (2016)
  • Author(s): Ohue Y, Kurose K, Nozawa R, Isobe M, Nishio Y, Tanaka T, Doki Y, Hori T, Fukuoka J, Oka M, Nakayama E.
  • Journal Title: Clinical Cancer Research Volume: 4 Pages: 1049-1060
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of two types of mite-allergen induced murine models of chronic asthma with different severity. (2016)
  • Author(s): Ikeda M, Katoh S, Shimizu H, Oka M.
  • Journal Title: Kawasaki Medical Journal Volume: 42 Pages: 1-7
  • NAID: 110010041931
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pulmonary M. scrofulaceum disease showing false-positive response of anti-GPL core IgA antibody. (2016)
  • Author(s): Kobashi Y, Mouri K, Kato S, Oka M.
  • Journal Title: Infection Diseases (Lond) Volume: 48 Pages: 767-768
  • Peer Reviewed / Open Access
• [Journal Article] Drug fever after cancer chemotherapy is most commonly observed on post treatment days 3-4. (2016)
  • Author(s): Ogawara D, Fukuda M, Ueno S, Ohue Y, Takemoto S, Mizoguchi K, Nakatomi K, Nakamura Y, Obase Y, Honda T, Tsukamoto K, Ashizawa K, Oka M, Kohno S.
  • Journal Title: Supportive Care in Cancer Volume: 24 Issue: 2 Pages: 615-619
  • DOI: 10.1007/s00520-015-2820-8
  • Peer Reviewed / Open Access
• [Journal Article] Chemotherapy (2015)
  • Author(s): Kasai T, Nakamura Y, Fukuda M, Kitazaki T, Nagashima S, Takatani H, Nakano H, Nakatomi K, Ikeda T, Yamaguchi H, Tsukamoto K, Oka M, Kohno S.
  • Journal Title: Phase II study of S-1 for previously untreated elderly patients with advanced non-small cell lung cancer. Volume: 61 Issue: 2 Pages: 93-98
  • DOI: 10.1159/000441486
  • Peer Reviewed / Open Access
• [Journal Article] Phase Ia study of FoxP3+ CD4 Treg depletion by infusion of a humanized anti-CCR4 antibody, KW-0761, in cancer patients. (2015)
  • Author(s): Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, Doi T, Suzuki S, Isobe M, Funakoshi T, Kakimi K, Nishikawa H, Udono H, Oka M, Ueda R, Nakayama E.
  • Journal Title: Clinical Cancer Research Volume: 21 Pages: 4327-4336
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Contrasting effects of the cytotoxic anticancer drug Gemcitabine and the EGFR tyrosine kinase inhibitor Gefitinib on NK cell-mediated cytotoxicity via regulation of NKG2D ligand in non-small-cell lung cancer cells. (2015)
  • Author(s): Okita R, Wolf D, Yasuda K, Maeda A, Yukawa T, Saisho S, Shimizu K, Yamaguchi Y, Oka M, Nakayama E, Lundqvist A, Kiessling R, Seliger B, Nakata M.
  • Journal Title: PLoS One Volume: 10 Issue: 10 Pages: e0139809-e0139809
  • DOI: 10.1371/journal.pone.0139809
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical significance of humoral immunity against XAGE1 cancer-testis antigen in lung adenocarcinoma. (2018)
  • Author(s): Oka M, Kurose K, Isobe M, Fukuda M, Ohue Y.
  • Organizer: ASCO-SITC (American Society of Clinical Oncology - Society for Immunotherapy of Cancer)
  • Int'l Joint Research
• [Presentation] Correlation of Clinical Response and XAGE1 Immunity in Lung Adenocarcinoma. (2017)
  • Author(s): Ohue Y, Kurose K, Isobe M, Fukuda M, Nakayama E, Oka M.
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Reviving Chemotherapy Sensityvity after Anti-CCR4 mAb (Mogamulizumab) Treatment in Lung Cancer Patients. (2017)
  • Author(s): Kurose K, Ohue Y, Isobe M, Suzuki S, Wada H, Ueda R, Nakayama E, Oka M.
  • Organizer: IASLC 18th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Reviving chemotherapy sensitivity after anti-CCR4 mAb (mogamulizumab) treatment in lung cancer patients. (2017)
  • Author(s): Kurose K, Ohue Y, Isobe M, Suzuki S, Wada H, Oka M, Ueda R, Nakayama E.
  • Organizer: Third CRI-CIMT-EATI-AACR Second International Cancer Immunotherapy Conference
  • Int'l Joint Research
• [Presentation] Immuno-inhibitory pathway, TIM-3/Galectin-9, in lung adenocarcinoma: clinical and in vitro analysis. (2017)
  • Author(s): Oka M, Ohue Y, Kurose K, Nishio Y, Isobe M, Nakayama E.
  • Organizer: 101st Annual Meeting of American Association of Cancer Research (AACR)
  • Int'l Joint Research
• [Presentation] 肺腺癌のTIM-3/Galectin-9経路を介した免疫抑制と予後 (2016)
  • Author(s): 黒瀬浩史、大植祥弘、磯辺みどり、中山睿一、岡 三喜男
  • Organizer: 第57回日本肺癌学会総会
  • Place of Presentation: 福岡国際会議場（福岡市）
  • Year and Date: 2016-12-19
• [Presentation] Role of TIM-3/Galectin-9 pathway in lung adenocarcinoma. (2016)
  • Author(s): Ohue Y, Kurose K, Nishio Y, Isobe M, Oka M, Nakayama E.
  • Organizer: CRI-CIMT-EATI-AACR Second International Cancer Immunotherapy Conference
  • Place of Presentation: Nw York（米国）
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] Phase Ⅰa study of FoxP3+ CD4 Treg depletion by infusion of a humanized anti-CCR4 antibody, KW-0761, in cancer patients. (2015)
  • Author(s): Kurose K, Ohue Y, Wada H, Doi T, Nishikawa H, Oka M, Ueda R.
  • Organizer: The Inaugural International Cancer Immunotherapy Conference
  • Place of Presentation: New York（米国）
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] Discriminant function for predicting survival of lung adenocarcinoma patients developed by using immune parameters of PD-L1,Gal-9, and XAGE1 expression on tumor cells and T cell infiltration score. (2015)
  • Author(s): Ohue Y, Kurose K, Oka M, Nakayama E.
  • Organizer: The Inaugural International Cancer Immunotherapy Conference
  • Place of Presentation: New York（米国）
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Book] 読んで見てわかる免疫腫瘍学 (2017)
  • Author(s): 岡 三喜男
  • Total Pages: 170
  • Publisher: 中外医学社
  • ISBN: 9784498022645
• [Remarks] 川崎医科大学呼吸器内科ホームページ
• [Remarks] 川崎医科大学呼吸器内科（肺がん免疫研究室）ホームページ
  • URL: http://www.kawasaki-m.ac.jp/resp/
• [Remarks] 肺がん免疫研究室
  • URL: http://www.kawasaki-m.ac.jp/resp/
• [Patent(Industrial Property Rights)] がん治療効果の検査方法及び免疫応答誘導用組成物 (2017)
  • Inventor(s): 大植祥弘、黒瀬浩史、岡 三喜男、中山 睿一
  • Industrial Property Rights Holder: 大植祥弘、黒瀬浩史、岡 三喜男、中山 睿一
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-094986
  • Filing Date: 2017