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

2013 Fiscal Year Final Research Report

• 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
• 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

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] 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] 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) Pages: E649-58
  • 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 (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
• [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/