Establishment of an antibody that targets carbohydrate structures specific to metastatic gynaecological malignancies

• Project/Area Number: 24592530
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: Suzuki Atsushi 慶應義塾大学, 医学部, 助教 (00255514)
• Co-Investigator(Kenkyū-buntansha): TOMINGA Eiichiro 慶應義塾大学, 医学部, 講師 (80276328) ; SUZUKI Masami 慶應義塾大学, 医学部, 研究員 (10276321)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖鎖抗原 / 抗体 / 抗体療法 / 婦人科腫瘍

Outline of Final Research Achievements

We established the humanized HMMC-1 antibody which recognizes gynecologic cancers and demonstrates specific anti-tumor activity towards endometrial cancer. In vitro, the antibody demonstrated anti-tumor activity towards endometrial cancer cells with differing lymph node metastasis potential and demonstrated even greater cell proliferation inhibitory effects towards the cell line with greater metastatic potential. Cell cycle analysis demonstrated that this difference in proliferation inhibition was not due to differences in proliferation or cell cycle. In addition, we elucidated the carbohydrate antigen recognized by the HMMC-1 antibody. Using mass spectrometry, we showed that the HMMC-1 antibody recognizes CD 166 and CD 49. Our research thus delineates the future possibility of clinical treatments based on HMMC-1 antibody administration as molecular target therapy towards endometrial cancer cases that demonstrate elevated CD 166 expression levels.

Research Products

• [Journal Article] Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients (2015)
  • Author(s): Yoshihama T, Chiyoda T, Kataoka F, Nomura H, Iguchi Y, Hashimoto S, Yamagami W, Tominaga E, Susumu N, Tsuda H, Aoki D.
  • Journal Title: Eur J Gynaecol Oncol Volume: 36 (4) Pages: 424-427
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Risk-reducing surgery in hereditary gynecological cancer: Clinical applications in Lynch syndrome and hereditary breast and ovarian cancer. (2015)
  • Author(s): Adachi M, Banno K, Yanokura M, Iida M, Nakamura K, Nogami Y, Umene K, Masuda K, Kisu I, Ueki A, Hirasawa A, Tominaga E, Aoki D.
  • Journal Title: Molecular and Clinical Oncology Volume: 3(2) Issue: 2 Pages: 267-273
  • DOI: 10.3892/mco.2014.460
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Drug repositioning for gynecologic tumors: a new therapeutic strategy for cancer (2015)
  • Author(s): Banno K, Iida M, Yanokura M, Irie H, Masuda K, Kobayashi Y, Tominaga E, Aoki D.
  • Journal Title: ScientificWorldJournal Volume: 2015 Issue: 1 Pages: 341362-341362
  • DOI: 10.1155/2015/341362
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers. (2015)
  • Author(s): Kobayashi Y, Nakamura K, Nomura H, Banno K, Irie H, Adachi M, Iida M, Umene K, Nogami Y, Masuda K, Kisu I, Ueki A, Yamagami W, Kataoka F, Hirasawa A, Tominaga E, Susumu N, Aoki D.
  • Journal Title: International Journal of Gynecological Cancer Volume: 25(3) Issue: 3 Pages: 440-446
  • DOI: 10.1097/igc.0000000000000377
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer (2015)
  • Author(s): Umene K, Yanokura M, Banno K, Irie H, Adachi M, Iida M, Nakamura K, Nogami Y, Masuda K, Kobayashi Y, Tominaga E, Aoki D
  • Journal Title: Int J Oncol. Volume: 46(4) Issue: 4 Pages: 1498-506
  • DOI: 10.3892/ijo.2015.2842
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia. (2015)
  • Author(s): Hirasawa A, Makita K, Akahane T, Yamagami W, Makabe T, Yokota M, Horiba Y, Ogawa M, Yanamoto S, Deshimaru R, Tominaga E, Banno K, Susumu N, Aoki D
  • Journal Title: Jpn J Clin Oncol Volume: 45(1) Issue: 1 Pages: 127-31
  • DOI: 10.1093/jjco/hyu164
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis. (2014)
  • Author(s): Sugihara K, Kobayashi Y, Suzuki A, Tamura N, Motamedchaboki K, Huang CT, Akama TO, Pecotte J, Frost P, Bauer C, Jimenez JB Jr, Nakayama J, Aoki D, Fukuda MN.
  • Journal Title: Nature Communications Volume: 5:4478 Issue: 1 Pages: 1-9
  • DOI: 10.1038/ncomms5478
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glycan profiling of gestational choriocarcinoma using a lectin microarray (2014)
  • Author(s): Kobayashi Y, Masuda K, Banno K, Kobayashi N, Umene K, Nogami Y, Tsuji K, Ueki A, Nomura H, Sato K, Tominaga E, Shimizu T, Saya H, Aoki D
  • Journal Title: Oncology Reports Volume: 31 Issue: 3 Pages: 1121-1131
  • DOI: 10.3892/or.2014.2979
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells (2013)
  • Author(s): Oikawa F, Kojima-Aikawa K, Inoue F, Suzuki A, Tanaka K, Tominaga E, Aoki D.
  • Journal Title: Cancer Science Volume: 104(1) Issue: 1 Pages: 62-9
  • DOI: 10.1111/cas.12038
  • Peer Reviewed
• [Journal Article] In vivo regulation of steroid hormones by the chstl0 sulfotransferase in mouse (2013)
  • Author(s): 鈴木-姉小路 美沙、他
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 7 Pages: 5007-5016
  • DOI: 10.1074/jbc.m112.433474
  • Peer Reviewed
• [Journal Article] Gene expression profile of a newly established choriocarcinoma cell line, iC(3)-1, compared to existing choriocarcinoma cell lines and normal placenta. (2013)
  • Author(s): Kobayashi Y, Banno K, Shimizu T, Ueki A, Tsuji K, Masuda K, Kisu I, Nomura H, Tominaga E, Nagano O, Saya H, Aoki D.
  • Journal Title: Placenta Volume: 34 Issue: 2 Pages: 110-118
  • DOI: 10.1016/j.placenta.2012.11.003
  • Peer Reviewed
• [Journal Article] The origin of stroma surrounding epithelial ovarian cancer cells. (2013)
  • Author(s): Akahane T, Hirasawa A, Susumu N, et al.
  • Journal Title: Int J Gynecol Pathol Volume: 32 Issue: 1 Pages: 26-30
  • DOI: 10.1097/pgp.0b013e3182518533
  • Peer Reviewed
• [Journal Article] HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells (2013)
  • Author(s): Oikawa F, Kojima-Aikawa K, Inoue F, Suzuki A, Tanaka K, Tominaga E, Aoki D
  • Journal Title: Cancer Sci. Volume: 104 (1) Pages: 62-69
  • Peer Reviewed
• [Journal Article] In vivo regulation of steroid hormones by the Chst10 sulfotransferase in mouse (2013)
  • Author(s): Suzuki-Anekoji M, Suzuki A, We SW, Angata K, Murai KK, Sugihara K, Akama TO, Khoo KH, Nakayama J, Fukuda MN, Fukuda M
  • Journal Title: J. Biol. Chem Volume: 288 (7) Pages: 5007-5016
  • Peer Reviewed
• [Presentation] Investigation of double cancer arising in young patients with endometrial cancer who receive fertility-preserving hormonal therapy using medroyprogesterone acetate. (2015)
  • Author(s): Nobuyuki Susumu, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Yoshikazu Ichikawa, Aya Takigawa, Atsushi Suzuki, Eiichiro Tominaga, Daisuke Aoki.
  • Organizer: 19th International Meeting of the European Society of Gynecological Oncology.
  • Place of Presentation: Nice, France
  • Year and Date: 2015-10-15
  • Int'l Joint Research
• [Presentation] Usefulness of intra-operative touch imprinting cytology of sentinel lymph nodes in endometrial cancer for improving intraoperative diagnostic accuracy (2015)
  • Author(s): Nobuyuki Susumu, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Yoshikazu Ichikawa, Aya Takigawa, Atsushi Suzuki, Eiichiro Tominaga, Daisuke Aoki
  • Organizer: 39th European Congress of Cytology
  • Place of Presentation: Milan, Italy
  • Year and Date: 2015-09-20
  • Int'l Joint Research
• [Presentation] A highly allosteric AKT inhibitor shows potent antiproliferative activity in combination with carboplatin and placlitaxel on malignant ascites cells from patients with ovarian cancer. (2015)
  • Author(s): Eiichiro Tominaga, Nobuyuki Susumu, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Atsushi Suzuki, Daisuke Aoki
  • Organizer: 39th European Congress of Cytology
  • Place of Presentation: Milan, Italy
  • Year and Date: 2015-09-20
  • Int'l Joint Research
• [Presentation] HNF1β protein expression in ovarian clear cell adenocarcinoma cell (2014)
  • Author(s): 冨永英一郎、鈴木淳、青木大輔
  • Organizer: 38th European congress of cytology
  • Place of Presentation: スイス・ジュネーブ
  • Year and Date: 2014-09-27 – 2014-09-30
• [Presentation] 血中の微量バイオマーカー分子由来ペプチドの効率的な精製にA2Mの関与が示唆される (2014)
  • Author(s): 青木豊、鈴木淳、遠山敦彦、嶋田崇史、青木大輔、佐藤孝明
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Multiplexed quantification of biomarker candidates by mass spectrometry for early-detection of ovarian cancer (2013)
  • Author(s): A Toyama, A Suzuki, T Shimada, Y Aoki, D Aoki, T Sato
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Review of cases of ovarian borderline tumors with tumor-derived atypical cells in peritoneal cytology (2013)
  • Author(s): Iguchi Y, Kataoka F, Nomumra H, Tsuda H, Chiyoda T, Hashimoto S, Takigawa A, Kuwahata M, Yamagami W, Tominaga E, Susumu N, Aoki D
  • Organizer: International Congress of Cytology
  • Place of Presentation: Palais de Congress, Paris, France
• [Presentation] The diagnostic significance of hysteroscopy in the preoperative diagnosis of endometrial cancer compared with cytologic and histologic examination. (2013)
  • Author(s): Takigawa A, Susumu N, Kuwahata M, Hashimoto S, Iguchi Y, Chiyoda T, Yamagami W, Nomura H, Kataoka F, Tominaga E, Suzuki A, Banno K, Aoki D
  • Organizer: International Congress of Cytology
  • Place of Presentation: Palais de Congress, Paris, France
• [Presentation] 上皮性卵巣癌におけるGNAS遺伝子の意義とその関連タンパクであるGSαの発現 (2012)
  • Author(s): 冨永 英一郎、鈴木 淳
  • Organizer: 第64回日本産婦人科学会学術集会
  • Place of Presentation: 神戸ポートピアホテル
• [Presentation] 子宮内膜がん細胞の転移性獲得におけるCD166/ALCAMの関与 (2012)
  • Author(s): 笈川 文子、鈴木 淳
  • Organizer: 第85回日本生化学学会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡