Development of CAR-T therapy targeting amino acid transporter SLC7A1 against colorectal cancer

2019 Fiscal Year Annual Research Report

• Project/Area Number: 16K10476
• Research Institution: Juntendo University
• Principal Investigator: 坂本 一博 順天堂大学, 医学部, 教授 (60205763)
• Co-Investigator(Kenkyū-buntansha): 小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982) ; 神山 博彦 順天堂大学, 医学部, 助教 (00365595)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: イオントランスポーター / モノクローナル抗体 / 抗体医薬 / 大腸癌 / 膜分子

Outline of Annual Research Achievements

本研究は、陽イオントランスポーターSLC7A1を標的とした大腸癌の新治療法開発を目的とするものである。申請者らは大腸癌組織特異的に高発現の遺伝子を探索し、複数の膜遺伝子を特定した。このうち14回膜貫通型の分子であるSLC7A1タンパクが、大腸癌組織において発現頻度・発現レベルとも高いこと、さらにこの遺伝子のsiRNA処理により大腸癌細胞株の増殖が阻害されることなどを確認した。本研究ではラットを用い抗SLC7A1抗体を高発現するハイブリドーマ細胞の作成、選抜等を経て、複数の抗SLC7A1モノクローナル抗体を取得した。取得した抗体を用いて免疫染色法により患者大腸癌組織での高発現を検出、また大腸癌細胞株を用いて抗体依存細胞障害活性を確認するなどの成果を得ている。
本研究の結果から、大腸癌の治療標的としての膜タンパクSLC7A1、また抗SLC71抗体を利用した新薬、新治療法の有望性が示されたといえる。

Research Products

• [Journal Article] Metastatic seeding of human colon cancer cell clusters expressing the hybrid epithelial/mesenchymal state. (2020)
  • Author(s): Mizukoshi K, Okazawa Y, Haeno H, Koyama Y, Sulidan K, Komiyama H, Saeki H, Ohtsuji N, Ito Y, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K and Orimo A.
  • Journal Title: Int J Cancer Volume: 146 Pages: 2547-2562
  • DOI: 10.1002/ijc.32672
  • Peer Reviewed / Open Access
• [Journal Article] Experience in the use of a device to attach an anti-adhesion-absorption barrier film to the abdominal cavity in laparoscopic colorectal surgery. (2020)
  • Author(s): Kojima Y, Sakamoto K, Tomiki Y, Mizukoshi K.
  • Journal Title: J Minim Access Surg Volume: - Pages: 1-2
  • DOI: 10.4103/jmas.JMAS_226_19
  • Peer Reviewed / Open Access
• [Journal Article] Using the polymeric circulating tumor cell chip to capture circulating tumor cells in blood samples of patients with colorectal cancer (2020)
  • Author(s): Kure K, Hosoya M, Ueyama T, Fukaya M, Sugimoto K, Tomiki Y,Ohnaga T, Sakamoto K, Komiyama H.
  • Journal Title: Oncl Lett Volume: 19 Pages: 2286-2294
  • DOI: 10.3892/ol.2020.11335
  • Peer Reviewed / Open Access
• [Journal Article] Angiopoietin-2 as a Prognostic Factor in Patients with Incurable Stage IV Colorectal Cancer. (2020)
  • Author(s): Munakata S, Ueyama T, Ishihara H, Komiyama H, Tsukamoto R, Kawai M, Takahashi M, Kojima Y, Tomiki Y,
  • Journal Title: J Gastrointest Cancer Volume: - Pages: 1-6
  • DOI: 10.1007/s12029-020-00392-1
  • Peer Reviewed / Open Access
• [Journal Article] A Trial protocol of biweekly TAS-102 and Bevacizumab as third-line chemotherapy for advanced/recurrent colorectal cancer: A phase II multicenter clinical trial (The TAS-CC4 Study). (2019)
  • Author(s): Yoshida Y, Yamada T, Matsuoka H, Sonoda H, Fukazawa A, Yoshida H, Ishida H, Hirata K, Hasegawa S, Sakamoto K, Otsuka T, Koda K.
  • Journal Title: J Anus Rectum Colon Volume: 3(3) Pages: 136-141
  • DOI: 10.23922/jarc.2018-043
  • Peer Reviewed / Open Access
• [Journal Article] Current status of venous thromboembolism development during the perioperative period for colorectal cancer, its prevention with enoxaparin, and monitoring methods. (2019)
  • Author(s): Aoki J, Sakamoto K, Takahashi R, Niwa K, Ishiyama S, Sugimoto K, Kamiyama H, Takahashi M, Kojima Y, Goto M, Tomiki Y, Iba T.
  • Journal Title: Ther Clin Risk Manag Volume: 15 Pages: 791-802
  • DOI: 10.2147/TCRM.S201954
  • Peer Reviewed / Open Access
• [Journal Article] Significance of serum p53 antibody as a tumor marker in colorectal cancer. (2019)
  • Author(s): Takahashi R, Sakamoto K, Sugimoto K, Motegi S, Tsukamoto R, Ichikawa R, Okazawa Y, Aoki J, Ishiyama S, Takahashi M, Kojima Y, Okuzawa A, Tomiki Y, Matsuoka J.
  • Journal Title: Dis Markers Volume: 2019:2721876 Pages: 1-6
  • DOI: 10.1155/2019/2721876
  • Peer Reviewed / Open Access
• [Journal Article] Effects of receptor for advanced glycation end-products (RAGE) signaling on intestinal ischemic damage in mice. (2019)
  • Author(s): Makino Y, Munakata S, Ueyama T, Honjo H, Kawano S, Takahashi M, Kojima Y, Tomiki T, Sakamoto K.
  • Journal Title: Eur Surg Res Volume: 60(5-6) Pages: 239-247
  • DOI: 10.1159/000504751
  • Peer Reviewed / Open Access
• [Journal Article] Experience of using a spray-type anti-adhesion barrier in laparoscopic surgery for colorectal cancer. (2019)
  • Author(s): Kojima Y, Sakamoto K, Okuzawa A.
  • Journal Title: J Surg Case Rep Volume: 2019(3)rjz085 Pages: 1-3
  • DOI: 10.1093/jscr/rjz085
  • Peer Reviewed / Open Access
• [Journal Article] Study on the efficacy of Daikenchuto on bowel motility after laparoscopic resection of colorectal cancer. (2019)
  • Author(s): Kojima Y, Sakamoto K, Tomiki Y, Nagakari K, Okuzawa A, Takahashi M, Kamiyama H, Ishiyama S, Sugimoto K, Munakata S, Kawai M, Mizukosi K, Okazawa Y.
  • Journal Title: World J Surg Surg Res Volume: 2(1128) Pages: 1-6
  • Peer Reviewed / Open Access
• [Journal Article] Cases of low anterior resection and ileostomy for rectal cancer that required more than 18 months for stoma closure. (2019)
  • Author(s): Kojima Y, Sakamoto K, Tomiki Y, Takahashi R, Tsukamoto R, Hagiwara T, Nagakari K.
  • Journal Title: J Surg Case Rep Volume: 2019(5):rjz153 Pages: 1-3
  • DOI: 10.1093/jscr/rjz153
  • Peer Reviewed / Open Access
• [Journal Article] DNA Methylation genome-wide analysis in remnant and primary gastric cancers. (2019)
  • Author(s): Sugimoto K, Ito T, Hulbert A, Chen C, Orita H, Maeda M, Moro H, Fukagawa T, Ushijima T, Katai H, Wada R, Sato K, Sakamoto K, Yu W, Considine M, Cope L, Brock MV.
  • Journal Title: Gastric Cancer Volume: 22(6) Pages: 1109-1120
  • DOI: 10.1007/s10120-019-00949-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum oxidative stress is an independent prognostic marker in colorectal cancer. (2019)
  • Author(s): Sugimoto K, Sakamoto K, Kawai M, Kawano S, Munakata S, Ishiyama S, Takahashi M, Kojima Y and Tomiki Y.
  • Journal Title: Transl Cancer Res Volume: 8(5) Pages: 1699-1708
  • DOI: 10.21037/tcr.2019.08.15
  • Peer Reviewed / Open Access
• [Journal Article] Study Protocol of regorafenib escalation for colorectal cancer (RECC): A Phase II Multicenter clinical trial of the efficacy and safety of regorafenib dose escalation therapy as the third or fourth line therapy for unresectable/recurrent colorectal cancer. (2019)
  • Author(s): Sugimoto K, Yamada T, Ishiyama S, Nakamura M, Yoshida Y, Hasegawa S, Yokomizo H, Naritaka Y, Sakuyama N, Ochiai t, Sonoda H, Tani M, Enomoto M, Katsumata K, Yamaguchi T, Ohta R, Ishimaru K, Watanabe Y, Koda K, Sakamoto K.
  • Journal Title: Juntendo Med J Volume: 65(1) Pages: 85-91
  • DOI: 10.14789/jmj.2019.65.JMJ18-SP01
  • Peer Reviewed / Open Access
• [Presentation] Stoma-related complications with permanent colostomy after laparoscopic abdominoperineal resection (APR) for rectal tumor. (2019)
  • Author(s): Sakamoto K, Okazawa Y, Mizukoshi K, Munakata S, Kawai M, Ishiyama S, Sugimoto K, Kamiyama H, Takahashi M, Kojima Y, Tomiki Y.
  • Organizer: ASCRS Annual Scientific Meeting in Cleveland, OH.
  • Int'l Joint Research
• [Presentation] Temporary diverting stoma at the time of the rectal cancer operation. (2019)
  • Author(s): Kojima Y, Sakamoto K, Tomiki Y, Okuzawa A, Takahashi M, Sugimoto K, Kawai M, Okazawa Y, Mizukoshi K, Makino Y, Amemiya K, Hagiwara T, Fukunaga T. Multimodal analgesia using acetaminophen for laparoscopic colorectal cancer surgery.
  • Organizer: The 27th International Congress of the European Association for Endoscopic Surgery, Sevilla, Andalucia.
  • Int'l Joint Research
• [Presentation] A study of complications after robotic surgery for rectal cancer. (2019)
  • Author(s): Tsuchiya Y, Okazawa Y, Mizukoshi K, Kawai M, Sugimoto K, Kamiyama H, Takahashi M, Kojima Y, Tomiki Y, Fukunaga T, Kajiyama Y, Sakamoto K.
  • Organizer: 2019 European Association for Endoscopic Surgery -Spain.
  • Int'l Joint Research
• [Presentation] Circulating plasma dna methylation status of tumor suppressor genes may be a biomarker of lung metastasis in colorectal cancer. (2019)
  • Author(s): Sugimoto K, Amemiya K, Tsuchiya Y, Hagiwara T, Matsuzawa T, Makino Y, Motegi S, Tsukamoto R, Kawai M, Kawano S, Niwa K, Ishiyama S, Kamiyama H, Takahashi M, Kojima Y, Tomiki Y, Fukunaga T, Kajiyama Y, Kawasaki S, Sakamoto K.
  • Organizer: Digestive Disease Week 2019, San Diego, USA.
  • Int'l Joint Research
• [Presentation] 局所進行直腸癌に対する術前化学療法の意義. (2019)
  • Author(s): 百瀨裕隆, 土谷祐樹, 牧野有里香, 茂木俊介, 青木順, 岡澤裕, 水越幸輔, 宗像慎也, 河野眞吾, 河合雅也, 石山隼, 杉本起一, 神山博彦, 髙橋玄, 小島豊, 奥澤淳司, 冨木裕一, 坂本一博.
  • Organizer: 第90回大腸癌研究会，京都.
• [Presentation] 大腸癌における癌抑制遺伝子の血漿中遊離DNAメチル化測定の意義. (2019)
  • Author(s): 杉本起一, 岡澤 裕, 水越幸輔, 河合雅也, 宗像慎也, 神山博彦, 高橋 玄, 小島 豊, 冨木裕一, 坂本一博.
  • Organizer: 第74回日本消化器外科学会総会, 東京.
• [Presentation] 網羅的解析を用いた新規結腸癌診断マーカーの探索. (2019)
  • Author(s): 塚本亮一, 小見山博光, 河野眞吾, 河合雅也, 高橋玄, 小島豊, 冨木裕一, 坂本一博.
  • Organizer: 第57回日本癌治療学会学術集会, 福岡.
• [Presentation] 大腸癌における原発巣および血漿中遊離DNAのCHFR遺伝子メチル化測定の意義. (2019)
  • Author(s): 杉本起一, 百瀬裕隆, 岡澤 裕, 高橋里奈, 水越幸輔, 盧 尚志, 河合雅也, 宗像慎也, 神山博彦, 高橋 玄, 小島 豊, 冨木裕一, 福永 哲, 梶山美明, 坂本一博.
  • Organizer: 第57回日本癌治療学会学術集会, 福岡.
• [Presentation] 大腸癌におけるCHFR遺伝子の原発巣癌組織および血漿中遊離DNAメチル化測定の意義. (2019)
  • Author(s): 杉本起一, 百瀬裕隆, 雨宮浩太, 土谷祐樹, 萩原俊昭, 松澤宏和, 呉 一眞, 本庄薫平, 岡澤 裕, 高橋里奈, 水越幸輔, 盧 尚志, 河合雅也, 河野眞吾, 宗像慎也, 神山博彦, 高橋 玄, 小島 豊, 冨木裕一, 坂本一博.
  • Organizer: 第27回JDDW, 神戸.
• [Remarks] 順天堂大学大学院 下部消化管外科学
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/