Development of novel human antibody against malignant glioma-derived stem cell

2015 Fiscal Year Final Research Report

• Project/Area Number: 25430166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: Akiyama Yasuto 静岡県立静岡がんセンター(研究所), その他部局等, その他 (70222552)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 抗体医薬 / がん性幹細胞 / 悪性グリオーマ / ヒト化マウス / ヒトモノクローナル抗体

Outline of Final Research Achievements

We aimed with developing human monoclonal antibody against YKL-40 protein, which is specifically expressed on malignant glioma-derived stem cell line established at Shizuoka Cancer Center, using humanized NOG-IL-4 transgenic (TG) mice. After immunization of recombinant human YKL-40 protein to humanized NOG-IL-4 TG mice and verification of antibody titer elevation, 7 anti-YKL-40 antibody-bearing single B cells out of ten million oflymphocytes were identified and sebsequently 4 specific antibody cDNAs were successfully cloned. Finally, 3 human recombinat monoclonal antibodies against YKL-40 protein were obtained using expi293 cells transduced with antibody genes consisting of VH and VL gene. These antibodies have still weak binding affinity for YKL-40 protein, therefore affinity maturation process will be needed using a phage display system.

Free Research Field

腫瘍免疫学