Identification of novel tumor antigen by using autologous-tumor specific immune responses in thoracic malignancies

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: National Hospital Organization, Kyushu Cancer Center (2012-2013); University of Occupational and Environmental Health, Japan (2011)
• Principal Investigator: TAKENOYAMA Mitsuhiro 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, その他 (10309966)
• Co-Investigator(Kenkyū-buntansha): HANAGIRI Takeshi 産業医科大学, 医学部, 准教授 (30299614) ; URAMOTO Hidetaka 産業医科大学, 医学部, 講師 (90389445) ; SHIGEMATSU Yoshiki (10546469)
• Project Period (FY): 2011 – 2013
• Keywords: 呼吸器悪性腫瘍 / 腫瘍抗原 / CTL / 特異的免疫応答

Research Abstract

In order to developing immunotherapy as new modalities against thoracic malignancies with poor prognosis, it is important to analyze autologous tumor-specific immune responses. In this study, we induced several CTLs from patients with lung cancer, which are HLA-A2 or HLA-A24-restricted. Among them, CTL Clone 1 recognized the autologous large cell carcinoma cell line as well as allogenic lung cancer cell lines including adenocarcinoma and squamous cell carcinoma of the lung in an HLA-A24-restricted manner. cDNA clone coding antigen recognized by the CTL was isolated by cDNA expression cloning using cDNA library made from autologous tumor cells. These approaches will help us to develop new modalities for diagnosis and therapy for thoracic malignancies.

Research Products

• [Journal Article] IV.Clinical trial of immunotherapy for lung cancer (2013)
  • Author(s): Takenoyama M, Ichinose Y
  • Journal Title: Gan To Kagaku Ryoho Volume: 40 Pages: 1018-20
• [Journal Article] The first case of lung carcinosarcoma harboring in-frame deletions at exon19 in the EGFR gene (2013)
  • Author(s): Toyokawa G, Takenoyama M, Taguchi K, Arakaki K, Inamasu E, Toyozawa R, Kojo M, Shiraishi Y, Morodomi Y, Takenaka T, Hirai F, Yamaguchi M, Seto T, Leone A, Graziano P, Ichinose Y
  • Journal Title: Lung Cancer Volume: 81 Pages: 491-4
  • Peer Reviewed
• [Journal Article] Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Kuroda K, Baba T, Shiota H, Ichiki Y, Nagata Y, Yasuda M, Uramoto H, So T, Takenoyama M, Tanaka F
  • Journal Title: J Surg Res Volume: 181 Pages: e57-63
  • Peer Reviewed
• [Journal Article] Invited commentary on comparison of three measurements on computed tomography for the prediction of less invasiveness in patients with clinical stage I non-small cell lung cancer (2013)
  • Author(s): Ichinose Y, Takenoyama M
  • Journal Title: Ann Thorac Surg Volume: 95 Pages: 1884
  • Peer Reviewed
• [Journal Article] Preoperative concurrent chemoradiotherapy of S-1/cisplatin for stage III non-small cell lung cancer (2013)
  • Author(s): Yamaguchi M, Toyokawa G, Ohba T, Sasaki T, Kometani T, Hamatake M, Hirai F, Taguchi K, Yamanaka T, Seto T, Takenoyama M, Sugio K, Ichinose Y
  • Journal Title: Ann Thorac Surg Volume: 96 Pages: 1783-9
  • Peer Reviewed
• [Journal Article] An extremely rare case of small-cell lung cancer harboring variant 2 of the EML4-ALK fusion gene (2013)
  • Author(s): Toyokawa G, Takenoyama M, Taguchi K, Toyozawa R, Inamasu E, Kojo M, Shiraishi Y, Morodomi Y, Takenaka T, Hirai F, Yamaguchi M, Seto T, Shimokawa M, Ichinose Y
  • Journal Title: Lung Cancer Volume: 81 Pages: 487-90
  • Peer Reviewed
• [Journal Article] Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy (2013)
  • Author(s): Toyokawa G, Takenoyama M, Hirai F, Toyozawa R, Inamasu E, Kojo M, Morodomi Y, Shiraishi Y, Takenaka T, Yamaguchi M, Shimokawa M, Seto T, Ichinose Y
  • Journal Title: Int J Clin Oncol
  • Peer Reviewed
• [Journal Article] Dramatic response to crizotinib in an ALK-positive adenocarcinoma patient with disseminated intravascular coagulation (2013)
  • Author(s): Toyokawa G, Takenoyama M, Watanabe S, Toyozawa R, Inamasu E, Kojo M, Shiraishi Y, Morodomi Y, Takenaka T, Hirai F, Yamaguchi M, Taguchi K, Seto T, Ichinose Y
  • Journal Title: J Thorac Oncol. Volume: 8 Pages: e96-8
  • Peer Reviewed
• [Journal Article] Do mutations of the enhancer of zeste homolog 2 gene exist in small-cell lung cancer? (2013)
  • Author(s): Toyokawa G, Takenoyama M, Ichinose Y
  • Journal Title: J Thorac Oncol Volume: 8 Pages: e103
  • Peer Reviewed
• [Journal Article] Clinical significance of expression of cancer/testis antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Baba T, Uramoto H, So T, Yamada S
  • Journal Title: Anticancer research Volume: 33 Pages: 2123-8
  • Peer Reviewed
• [Journal Article] Clinical significance of the frequency of regulatory T cells in regional lymph node lymphocytes as a prognostic factor for non-small-cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Shinohara S, Takenaka M, Oka S, Chikaishi Y, Nagata Y, Iwata T, Uramoto H, So T, Tanaka F
  • Journal Title: Lung Cancer Volume: 81 Pages: 475-9
  • Peer Reviewed
• [Journal Article] Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer (2013)
  • Author(s): Hanagiri T, Shigematsu Y, Kuroda K, Baba T, Shiota H, Ichiki Y, Nagata Y, Yasuda M, Uramoto H, So T, Takenoyama M, Tanaka F
  • Journal Title: The Journal of surgical research Volume: 181 Pages: e57-63
  • Peer Reviewed
• [Journal Article] First case of combined small-cell lung cancer with adenocarcinoma harboring EML4-ALK fusion and an exon 19 EGFR mutation in each histological component (2012)
  • Author(s): Toyokawa G, Taguchi K, Ohba T, Morodomi Y, Takenaka T, Hirai F, Yamaguchi M, Seto T, Takenoyama M, Sugio K, Ichinose Y
  • Journal Title: J Thorac Oncol Volume: 7 Pages: e39-41
  • Peer Reviewed
• [Journal Article] Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes (2012)
  • Author(s): Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Ichiki Y, Yasuda M, Uramoto H, Takenoyama M, Yasumoto K, Tanaka F
  • Journal Title: Oncol Lett Volume: 4 Pages: 625-30
  • Peer Reviewed
• [Journal Article] Differences in sensitivity to tumor-specific CTLs between primary and metastatic esophageal cancer cell lines derived from the same patient (2012)
  • Author(s): Ichiki Y, Hanagiri T, Takenoyama M, Baba T, Nagata Y, Mizukami M, So T, Sugaya M, Yasuda M, Uramoro H, Yasumoto K
  • Journal Title: Surg Today Volume: 42 Pages: 272-9
  • Peer Reviewed
• [Journal Article] Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes (2012)
  • Author(s): Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Ichiki Y, Yasuda M, Uramoto H, Takenoyama M, Yasumoto K, Tanaka F
  • Journal Title: Oncology letters Volume: 4 Pages: 625-30
  • Peer Reviewed
• [Presentation] 非小細胞肺癌術後再発症例におけるEGFR遺伝子変異、EML4-ALK融合遺伝子検索の意義 (2013)
  • Author(s): 竹中朋祐,豊澤亮,稲益英子,豊川剛二,白石祥理,諸富洋介,平井文彦,山口正史,瀬戸貴司,竹之山光広,一瀬幸人
  • Organizer: 第66回日本胸部外科学会定期学術集会
  • Place of Presentation: 仙台
  • Year and Date: 20131016-19
• [Presentation] Impact of the epidermal growth factor receptor mutation status on the post-recurrence survival of patients with surgically resected non-small-cell lung cancerdagger (2013)
  • Author(s): Takenaka T, Takenoyama M, Yamaguchi M, Toyozawa R, Inamasu E, Kojo M, Toyokawa G, Yoshida T, Shiraishi Y, Morodomi Y, Hirai F, Taguchi K, Shimokawa M, Seto T, Ichinose Y
  • Organizer: The European Cancer Congress 2013
  • Place of Presentation: Amsterdam
  • Year and Date: 20130927-1001
• [Presentation] 手術可能な肺癌は全て手術しなくてはならないか?手術(治療)しなくてもよい肺癌はあるかPure GGOを呈する肺野小結節の切除に対する検討 (2013)
  • Author(s): 山口正史,豊川剛二,諸富洋介,豊澤亮,稲益英子,古城都,白石祥理,平井文彦,竹中朋祐,瀬戸貴司,竹之山光広,一瀬幸人
  • Organizer: 第30回日本呼吸器外科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20130509-10
• [Presentation] 肺癌集学的治療の新たな展開III期局所進行非小細胞肺癌に対するシスプラチン+S-1を用いた術前化学放射線同時併用療法の治療成績 (2013)
  • Author(s): 竹之山光広,豊澤亮,稲益英子,古城都,豊川剛二,白石祥理,諸富洋介,竹中朋祐,山口正史,瀬戸貴司,一瀬幸人
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20130411-13
• [Presentation] 肺癌所属リンパ節における制御性T細胞の臨床病理学的意義 (2012)
  • Author(s): 花桐武志,重松義紀,竹中賢,岡壮一,近石泰弘,下川秀彦,中川誠,永田好香,岩田輝男,浦本秀隆,宗知子,田中文啓
  • Organizer: 第53回日本肺癌学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20121108-09
• [Presentation] 肺癌所属リンパ節における制御性T細胞および微小リンパ節転移の解析 (2012)
  • Author(s): 花桐武志,重松義紀,竹中賢,岡壮一,近石泰弘,下川秀彦,中川誠,永田好香,浦本秀隆,宗知子,田中文啓
  • Organizer: 第50回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20121025-27
• [Presentation] 非小細胞肺癌における癌精巣抗原発現とワクチン療法への応用 (2012)
  • Author(s): 重松義紀,竹中賢,岡壮一,近石泰弘,馬場哲郎,下川秀彦,中川誠,浦本秀隆,宗知子,花桐武志,田中文啓
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20120412-14
• [Presentation] 悪性胸膜中皮腫に対する腫瘍特異的免疫応答の解析(第2報) (2012)
  • Author(s): 竹之山光広,重松義紀,馬場哲郎,永田好香,浦本秀隆,宗知子,花桐武志,田中文啓
  • Place of Presentation: 産業医科大学
  • Year and Date: 20120000
• [Presentation] Prognostic implications of HLA-class I expression in patients who underwent surgery for non-small cell lung cancer (2012)
  • Author(s): 花桐武志,重松義紀,黒田耕志,馬場哲郎,塩田広宣,市来嘉伸,永田好香,安田学,浦本秀隆,宗知子,竹之山光広,田中文啓
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] 新規悪性胸膜中皮腫関連抗原の機能解析と腫瘍マーカーとしての意義 (2011)
  • Author(s): 重松義紀,黒田耕志,馬場哲郎,竹中賢,近石泰弘,岡壮一,中川誠,下川秀彦,浦本秀隆,宗知子,花桐武志,田中文啓
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20111103-04
• [Presentation] CHP-MAGE-A4 vaccine for patients with advanced lung cancer (Phase I study) (2011)
  • Author(s): 花桐武志,重松義紀,馬場哲郎,永田好香,浦本秀隆,宗知子,竹之山光広,安元公正,田中文啓,影山慎一,珠玖洋
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-05