Development of cancer vaccines targeting the cancer/testis antigen XAGE highly-expressed in lung adenocarcinoma

• Project/Area Number: 23591169
• 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): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肺癌 / 癌精巣抗原 / 癌ワクチン / ペプチドワクチン / 癌免疫療法 / がん精巣抗原 / 肺がん / 腫瘍免疫 / がん免疫療法 / 予後因子 / がんワクチン / 制御性T細胞 / 抗体産生 / 臨床試験 / 免疫モニタリング / 免疫調節薬

Research Abstract

The spontaneous immune responses against XAGE-1b were analyzed in non-small cell lung cancer (NSCLC). An antibody response against XAGE-1b was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma. A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b antibody-positive patients. These responses of CD4 and CD8 T-cell against the XAGE-1b indicate the strong immunogenicity of the XAGE-1b antigen in NSCLC. We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b 18-31 peptide as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b 21-29 peptide as a CD8 T-cell epitope. The CD4 T-cell clone recognized DCs pulsed with the synthetic protein. The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b and the appropriate HLA class I allele. These findings establish XAGE-1b as a promising target for a lung cancer vaccine.

Research Products

• [Journal Article] Genetic variants of immunoglobulin gamma and kappa chains influence humoral immunity to the cancer-testis antigen XAGE-1b (GAGED2a) in patients with non-small cell lung cancer (2014)
  • Author(s): Pandey JP, Namboodiri AM, Ohue Y, Oka M, Nakayama E.
  • Journal Title: Clin Exp Immunol Volume: 176(1) Pages: 78-83
  • Peer Reviewed
• [Journal Article] TLR4 and NLRP3 inflammasome activation in monocytes by N-propionyl- cysteaminyl-phenolmaleimid-dextran (NPCMD) (2014)
  • Author(s): Mizote Y, Wakamatsu K, Ito S, Uenaka A, Ohue Y, Kurose K, Isobe M, Ito A, Tamura Y, Honda H, Yamashita T, Nohara S, Oka M, Jimbow K, Nakayama E.
  • Journal Title: J Dermatol Sci. Volume: 73(3) Pages: 209-15
  • Peer Reviewed
• [Journal Article] Production of NY-ESO-1 peptide /DRB1*08:03 tetramers and their use for ex vivo detection of CD4 T-cell responses in the vaccinated cancer patients (2014)
  • Author(s): Mizote, Y, Uenaka A, Isobe M, Wada H, Kakimi K, Saika T, Kita S, Koide Y, Oka M, Nakayama E.
  • Journal Title: Vaccine Volume: 32(8) Pages: 957-64
  • Peer Reviewed
• [Journal Article] Genetic variants of immunoglobulin γ and κ chains influence humoral immunity to the cancer-testis antigen XAGE-1b (GAGED2a) in patients with non-small cell lung cancer. (2014)
  • Author(s): Pandey JP, Namboodiri AM, Ohue Y, Oka M, Nakayama E.
  • Journal Title: Clinical Experimental Immunology Volume: 176 Issue: 1 Pages: 78-83
  • DOI: 10.1111/cei.12247
  • Peer Reviewed
• [Journal Article] Vaccination With NY-ESO-1 Overlapping Peptides Mixed With Picibanil OK-432 and Montanide ISA-51 in Patients With Cancers Expressing the NY-ESO-1 Antigen (2014)
  • Author(s): Wada H, Isobe M, Kakimi K, Mizote Y, Eikawa S, Sato E, Takigawa N, Kiura K, Tsuji K, Iwatsuki K, Yamasaki M, Miyata H, Matsushita H, Udono H, Seto Y, Yamada K, Nishikawa H, Pan L, Venhaus R, Oka M, Doki Y, Nakayama E.
  • Journal Title: J Immunother Volume: 37(2) Issue: 2 Pages: 84-92
  • DOI: 10.1097/cji.0000000000000017
  • Peer Reviewed
• [Journal Article] TLR4 and NLRP3 inflammasome activation in monocytes by N-propionyl cysteaminylphenol-maleimid-dextran (NPCMD). (2014)
  • Author(s): Mizote Y, Wakamatsu K, Ito S, Uenaka A, Ohue Y, Kurose K, Isobe M, Ito A, Tamura Y, Honda H, Yamashita T, Nohara S, Oka M, Jimbow K, Nakayama E.
  • Journal Title: Journal of Dermatological Science Volume: 73 Pages: 209-215
  • Peer Reviewed
• [Journal Article] Production of NY-ESO-1 peptide/DRB1*08:03 tetramers and their use for ex vivo detection of CD4 T-cell responses in the vaccinated cancer patients. (2014)
  • Author(s): Mizote, Y, Uenaka A, Isobe M, Wada H, Kakimi K, Saika T, Kita S, Koide Y, Oka M, Nakayama E.
  • Journal Title: Vaccine Volume: 32 Pages: 957-964
  • Peer Reviewed
• [Journal Article] Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide (2013)
  • Author(s): Eikawa S, Kakimi K, Isobe M, Kazushima K, Luescher I, Ohue Y, Ikeuchi K, Uenaka A, Nishikawa H, Udono H, Oka M, Nakayama E.
  • Journal Title: Int J Cancer Volume: 132(2) Pages: 345-54
  • Peer Reviewed
• [Journal Article] 抗CCR4抗体と制御性T細胞 (2013)
  • Author(s): 黒瀬浩史、大植祥弘、岡三喜男
  • Journal Title: 癌と化学療法 Volume: 第8巻第10号 Pages: 1150-1155
• [Journal Article] Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide. (2013)
  • Author(s): Eikawa, S., Kakimi, K., Idobe, M., Kuzushima, K., Luescher, I., Ohue, Y., Ikeuchi, K., Uenaka, A., Nishikawa, H., Udono, H., Oka, M., and Nakayama, E.
  • Journal Title: Int. J. Cancer Volume: 132(2) Issue: 2 Pages: 345-54
  • DOI: 10.1002/ijc.27682
  • Peer Reviewed
• [Journal Article] Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients (2012)
  • Author(s): Ohue Y, Eikawa S, Okazaki N, Mizote Y, Isobe M, Uenaka A, Fukuda M, Old LJ, Oka M, Nakayama E.
  • Journal Title: Int J Cancer Volume: 131(5)
  • Peer Reviewed
• [Journal Article] Spontaneous antibody, and CD4 and CD8T-cell responses against XAGE-1b(GAGED2a) in non-small cell lung cancer patients. (2012)
  • Author(s): Ohue, Y., Eikawa, S., Okazaki, N., Mizote, Y., Isobe, M., Uenaka, A., Fukuda M., Old, L.J., Oka, M., and Nakayama, E.
  • Journal Title: Int. J. Cancer Volume: 131(5) Issue: 5
  • DOI: 10.1002/ijc.27359
  • Peer Reviewed
• [Journal Article] A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing NY-ESO-1 antigen (2011)
  • Author(s): Kakimi K, Isobe M, Uenaka A, Wada H, Sato E, Doki Y, Nakajima J, Seto Y, Yamatsuji T, Oka M, Pan L, Hoffman EW, Old LJ, Nakayama E.
  • Journal Title: Int J Cancer Volume: 129(12) Pages: 2836-46
  • Peer Reviewed
• [Presentation] Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance (2013)
  • Author(s): 大植祥弘、黒瀬浩史、松本博文、阿部公亮、堅田洋佑、磯辺みどり、上中明子、中山睿一、岡三喜男
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-22
• [Presentation] Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb (2013)
  • Author(s): 黒瀬浩史、大植祥弘、堅田洋佑、阿部公亮、磯辺みどり、松本博文、上中明子、中山睿一、岡三喜男
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-22
• [Presentation] Prolonged overall survival in XAGE-1b (GAGED2a) antibody positive NSCLC patients (2013)
  • Author(s): Ohue Y, Kurose K, Mizote Y, Matsumoto H, Isobe M, Uenaka A, Fukuda M, Oka M, Nakayama E.
  • Organizer: 21st Annual Cancer Research Institute International Cancer Immunotherapy Symposium
  • Place of Presentation: New York, USA
  • Year and Date: 2013-10-01
• [Presentation] Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb (2013)
  • Author(s): Kurose K, Ohue Y, Mizote Y, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 21st Annual Cancer Research Institute International Cancer Immunotherapy Symposium
  • Place of Presentation: New York, USA
  • Year and Date: 2013-10-01
• [Presentation] Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance (2013)
  • Author(s): Ohue Y, Kurose K, Eikawa S, Mizote Y, Matsumoto H, Isobe M, Uenaka A, Fukuda M, Nakayama E, Oka M.
  • Organizer: 104th Annual Meeting of American Association of Cancer Research (AACR)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-04-07
• [Presentation] Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb (2013)
  • Author(s): Kurose K, Eikawa S, Mizote Y, Ohue Y, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 104th Annual Meeting of American Association of Cancer Research (AACR)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2013-04-07
• [Presentation] 非小細胞肺がん患者におけるXAGE-1b免疫の頻度と強さ (2012)
  • Author(s): 大植祥弘、榮川伸吾、黒瀬浩史、阿部公亮、橘高誠、池田征樹、清水大樹、毛利圭二、加藤茂樹、尾長谷靖、小橋吉博、中山睿一、岡三喜男
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-08
• [Presentation] 非小細胞肺癌患者における癌精巣抗原XAGE-1dに対する免疫応答 (2012)
  • Author(s): 松本博文、大植祥弘、榮川伸吾、溝手雄、磯辺みどり、上中明子、永安武、中山睿一、岡三喜男
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-08
• [Presentation] 肺癌患者における癌微小環境中の免疫応答の解析 (2012)
  • Author(s): 松本博文、大植祥弘、榮川伸吾、溝手雄、磯辺みどり、上中明子、永安武、中山睿一、岡三喜男
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-08
• [Presentation] Immune response to XAGE-1b(GAGED2a) in NSCLC patients and its clinical relevance (2012)
  • Author(s): Ohue Y, Eikawa S, Mizote Y, Matsumoto H, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 20th Annual International Cancer Immune- therapy Symposium
  • Place of Presentation: New York, USA
  • Year and Date: 2012-10-01
• [Presentation] Treg depletion from PBMCs by treatment with defucosylated anti- human CCR4 mAb (2012)
  • Author(s): Kurose K, Eikawa S, Mizote Y, Ohue Y, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 20th Annual International Cancer Immune- therapy Symposium
  • Place of Presentation: New York, USA
  • Year and Date: 2012-10-01
• [Presentation] Correlation of antibody and T-cell responses against XAGE-1b in NSCLC patients (2012)
  • Author(s): Ohue Y, Eikawa S, Mizote Y, Matsumoto H, Okazaki N, Isobe M, Uenaka A, Nakayama E, Oka M.
  • Organizer: 103rd Annual Meeting of American Association of Cancer Research (AACR)
  • Place of Presentation: Chicago, USA
  • Year and Date: 2012-04-01
• [Presentation] Immunogenicity of cancer/testis antigen XAGE-1d in patients with non-small- cell lung cancer (NSCLC) (2012)
  • Author(s): Matsumoto H, Ohue Y, Eikawa S, Mizote Y, Kurose K, Isobe M, Uenaka A, Nagayasu T, Oka M, Nakayama E.
  • Organizer: 103rd Annual Meeting of American Association of Cancer Research (AACR)
  • Place of Presentation: Chicago, USA
  • Year and Date: 2012-04-01
• [Presentation] Correlation of antibody and T-cell responses against XAGE-1b in NSCLC patients (2012)
  • Author(s): Ohue Y, Eikawa S, Mizote Y, Matsumoto H, Okazaki N, Isobe M, Uenaka A, Nakayama E, Oka M
  • Organizer: 103rd Annual Meeting of American Association of Cancer Research
  • Place of Presentation: McCormick Convention Center (Chicago, IL, USA)
• [Presentation] Immunogenicity of cancer/testis antigen XAGE-1d in patients with non-small-cell lung cancer (NSCLC) (2012)
  • Author(s): Matsumoto H, Ohue Y, Eikawa S, Mizote Y, Kurose K, Isobe M, Uenaka A, Nagayasu T, Oka M, Nakayama E.
  • Organizer: 103rd Annual Meeting of American Association of Cancer Research
  • Place of Presentation: McCormick Convention Center (Chicago, IL, USA)
• [Presentation] Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance (2012)
  • Author(s): Ohue Y, Eikawa S, Mizote Y, Matsumoto H, Isobe M, Uenaka A, Oka M, Nakayama E
  • Organizer: 20th Annual International Cancer Immunotherapy Symposium
  • Place of Presentation: Millennium Conference Center (New York, NY, USA)
• [Presentation] Treg depletion from PBMCs by treatment with defucosylated anti-human CCR4 mAb (2012)
  • Author(s): Kurose K, Eikawa S, Mizote Y, Ohue Y, Isobe M, Uenaka A, Oka M, Nakayama E
  • Organizer: 20th Annual International Cancer Immunotherapy Symposium
  • Place of Presentation: Millennium Conference Center (New York, NY, USA)
• [Presentation] Correlation of antibody and T-cell responses against XAGE-1b in NSCLC patients (2011)
  • Author(s): Ohue Y, Eikawa S, Mizote Y, Matsumoto H, Okazaki N, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 19th Annual Cancer Research Institute International Cancer Immunotherapy Symposium
  • Place of Presentation: New York, USA
  • Year and Date: 2011-10-03
• [Presentation] Induction of CD8 T Cell Responses Restricted to Multiple HLA Class I Alleles in a Cancer Patient by Immunization with a 20-Mer NY-DSO-1 91-110) Peptide (2011)
  • Author(s): Eikawa S, Kakimi K, Isobe M, Kuzushima K, Ohue Y, Ikeuchi K, Uenaka A, Udono H, Lloyd Old, Oka M and Nakayama E.
  • Organizer: 19th Annual Cancer Research Institute International Cancer Immunotherapy Symposium
  • Place of Presentation: New York, USA
  • Year and Date: 2011-10-03
• [Presentation] Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance.
  • Author(s): Ohue Y, Kurose K, Eikawa S, Mizote Y, Matsumoto H, Isobe M, Uenaka A, Fukuda M, Nakayama E, Oka M.
  • Organizer: 104th Annual Meeting of American Association of Cancer Research (AACR)
  • Place of Presentation: Convention Center, Washington DC, USA
• [Presentation] Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb.
  • Author(s): Kurose K, Eikawa S, Mizote Y, Ohue Y, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 104th Annual Meeting of American Association of Cancer Research (AACR)
  • Place of Presentation: Convention Center, Washington DC, USA
• [Presentation] Prolonged overall survival in XAGE-1b (GAGED2a) antibody positive NSCLC patients.
  • Author(s): Ohue Y, Kurose K, Mizote Y, Matsumoto H, Isobe M, Uenaka A, Fukuda M, Oka M, Nakayama E.
  • Organizer: 21st Annual Cancer Research Institute International Cancer Immunotherapy Symposium
  • Place of Presentation: Grand Hyatt New York, New York, NY, USA
• [Presentation] Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb.
  • Author(s): Kurose K, Ohue Y, Mizote Y, Isobe M, Uenaka A, Oka M, Nakayama E.
  • Organizer: 21st Annual Cancer Research Institute International Cancer Immunotherapy Symposium
  • Place of Presentation: Grand Hyatt New York, New York, NY, USA
• [Presentation] 次世代がん治療としての分子免疫療法
  • Author(s): 岡 三喜男
  • Organizer: 第53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
  • Invited
• [Presentation] Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance
  • Author(s): 大植祥弘、黒瀬浩史、松本博文、阿部公亮、堅田洋佑、磯辺みどり、上中明子、福田実、中山睿一、岡 三喜男
  • Organizer: 第54回 日本肺癌学会総会
  • Place of Presentation: ホテルニューオータニ東京、東京
• [Presentation] Correlation of antibody and T-cell responses against XAGE-1b in NSCLC patients
  • Author(s): Mikio Oka
  • Organizer: 19th Annual International Cancer Immunotherapy Symposium
  • Place of Presentation: Millennium Conference Center (New York, USA)
• [Remarks] 川崎医科大学呼吸器内科, がん免疫療法
  • URL: http://www.kawasaki-m.ac.jp/resp/
• [Remarks] 川崎医科大学呼吸器内科ホームページ
  • URL: http://www.kawasaki-m.ac.jp/resp/
• [Remarks]
  • URL: http://www.kawasaki-m.ac.jp/resp/