Clinical development of the next-generation cancer immunotherapy against lung adenocarcinoma

• Project/Area Number: 26830117
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Kawasaki Medical School
• Principal Investigator: OHUE YOSHIHIRO 川崎医科大学, 医学部, 講師 (70435014)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肺癌 / がん精巣抗原 / 抗体 / がん免疫 / 免疫 / 予後 / 腫瘍免疫 / がん抗原

Outline of Final Research Achievements

XAGE is a cancer/testis antigen expressed mainly in non-small cell lung cancer. In this study, we investigated correlation of intensity of humoral and cellular immune responses against XAGE1 and its clinical relevance. Frequency of XAGE1 antibody positive patients in NSCLC was 9.2% (46/500).The frequencies of Th1 and Th17 were significantly higher and immunosuppressive populations as activated Tregs and MDSC were significantly lower in antibody positive patients compared to antibody negative patients. Median OS were 31.5 and 15.6 months in antibody-positive and negative patients (P=0.006) with 145 stage IIIB/IV lung adenocarcinoma. Multivariable analyses showed XAGE1 antibody response was independent prognostic factor. Our findings indicate that XAGE1 antibody response is a prognostic biomarker in the patients with advanced lung adenocarcinoma.

Research Products

• [Journal Article] Drug fever after cancer chemotherapy is most commonly observed on posttreatment days 3 and 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: 2 Pages: 615-619
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increase of activated Treg in TIL in lung cancer and in vitro depletion of Treg by ADCC using an anti-human CCR4 mAb (KM2760). (2015)
  • Author(s): Koji Kurose, Yoshihiro Ohue, Eiichi Sato Akira Yamauchi, Shingo Eikawa, Midori Isobe, Yumi Nishio, Akiko Uenaka, Mikio Oka, and Eiichi Nakayama.
  • Journal Title: J Thorac Oncol. Volume: 10 Issue: 1 Pages: 74-83
  • DOI: 10.1097/jto.0000000000000364
  • Peer Reviewed / Open Access
• [Journal Article] Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia. (2015)
  • Author(s): Katoh S, Ikeda M, Shimizu H, Abe M, Ohue Y, Mouri K, Kobashi Y, Oka M.
  • Journal Title: Lung Volume: 5 Issue: 5 Pages: 683-689
  • DOI: 10.1007/s00408-015-9775-x
  • Peer Reviewed / Acknowledgement Compliant
• [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): 2.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: Clin Cancer Res. Volume: 21 Issue: 19 Pages: 4327-36
  • DOI: 10.1158/1078-0432.ccr-15-0357
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prolongation of overall survival in advanced lung adenocarcinoma patients with the XAGE1 (GAGED2a) antibody. (2014)
  • Author(s): Ohue Y, Kurose K, Mizote Y, Matsumoto H, Nishio Y, Isobe M, Fukuda M, Uenaka A, Oka M and Nakayama E.
  • Journal Title: Clin. Cancer Res. Volume: 20 (19) Issue: 19 Pages: 5052-5063
  • DOI: 10.1158/1078-0432.ccr-14-0742
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antibody response to cancer/testis (CT) antigens: A prognostic marker in cancer patients (2014)
  • Author(s): Yoshihiro Ohue, Hisashi Wada, Mikio Oka & Eiichi Nakayama
  • Journal Title: Oncoimmunology Volume: e970032 Issue: 11 Pages: e970032-e970032
  • DOI: 10.4161/21624011.2014.970032
  • Peer Reviewed
• [Presentation] Survival prediciting discriminant function with immune parameters for lung adenocarcinoma patients (2015)
  • Author(s): Yoshihiro Ohue, Koji Kurose, Yumi Nishio, Midori Isobe, Akiko Uenaka, Mikio Oka and Eiichi Nakayama
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-08
• [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): Yoshihiro Ohue, Koji Kurose, Yumi Nishio, Midori Isobe, Akiko Uenaka, Mikio Oka and Eiichi Nakayama
  • 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] Clinical effect of XAGE1(GAGED2a) antigen expression and antibody response in EGFR mutated and wild-type advanced lung adenocarcinoma (2015)
  • Author(s): 大植祥弘
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2015-04-17 – 2015-04-19
• [Presentation] Clinical effect of XAGE1(GAGED2a) antigen expression and antibody response in EGFR mutated and wild-type advanced lung adenocarcinoma (2015)
  • Author(s): Yoshihiro Ohue, Koji Kurose, Yumi Nishio, Midori Isobe, Akiko Uenaka, Mikio Oka and Eiichi Nakayama
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2015-04-17
• [Presentation] 肺腺癌でXAGE1に対する宿主免疫応答の解析と予後延長効果の証明 (2015)
  • Author(s): 大植祥弘
  • Organizer: 第112回日本内科学会講演会
  • Place of Presentation: みやこめっせ（京都府）
  • Year and Date: 2015-04-10 – 2015-04-12
• [Presentation] 肺腺癌でXAGE1に対する宿主免疫応答の解析と予後延長効果の証明 (2015)
  • Author(s): Yoshihiro Ohue, Koji Kurose, Yumi Nishio, Midori Isobe, Akiko Uenaka, Mikio Oka and Eiichi Nakayama
  • Organizer: 第112回日本内科学会講演会
  • Place of Presentation: みやこめっせ（京都）
  • Year and Date: 2015-04-10
• [Presentation] 進行期肺腺癌におけるXAGE1（GAGED2a）免疫と予後 (2015)
  • Author(s): 大植祥弘
  • Organizer: 第12回日本免疫治療学研究会学術集会
  • Place of Presentation: 東京ガーデンパレス（東京都）
  • Year and Date: 2015-02-28
  • Invited
• [Presentation] 非小細胞肺がん患者で、免疫グロブリンγ鎖およびκ鎖の遺伝的変異がXAGE1免疫に及ぼす影響 (2014)
  • Author(s): 大植祥弘
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府）
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] Clinical effect of XAGE1 (GAGED2a) antigen expression and antibody response in EGFR mutated and wild-type advanced lung adenocarcinoma (2014)
  • Author(s): 大植祥弘
  • Organizer: 22nd Annual International Cancer Immunotherapy Symposium
  • Place of Presentation: The Grand Hyatt New York（N.Y. USA）
  • Year and Date: 2014-10-06 – 2014-10-08
• [Patent(Industrial Property Rights)] 免疫因子を指標とした肺腺癌の予後演算式作成方法と予後推定方法 (2015)
  • 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: 2015-212393
  • Filing Date: 2015-10-28