Development of diagnostic method and its application to treatment in GIST with particular mutations through creating monoclonal antibodies

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05166
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hyogo Medical University
• Principal Investigator: Hirota Seiichi 兵庫医科大学, 医学部, 教授 (50218856)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: GIST / c-kit / PDGFRA / mutation / antibody

Outline of Final Research Achievements

Among the gene mutations observed in GISTs, Dup-502&503 of the c-kit gene, Asp842Val of the PDGFRA gene and Del-557&558 of the c-kit gene were targeted to make specific antibodies to use for image diagnosis and therapy. High titer fraction on ELISA was obtained, but the final products of specific antibodies for them were not gained. We also investigated the clinicopathological characteristics of GISTs in NF1 patients, effective neoadjuvant imatinib therapy for giant gastric GISTs and condition of management of high-risk GIST patients in the real world.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

GISTの治療はその病態解明に伴って劇的に進歩したが、分子標的治療に対する二次耐性の問題は患者のさらなる予後改善の足かせとなっている。GISTに特徴的なc-kit遺伝子やPDGFRA遺伝子の変異に対する特異的なモノクローナル抗体の作製が可能となれば、これまでの分子標的薬とは異なった機序で病気を制御できる可能性があり、画像診断にも応用できると考えたが、思いのほか抗体作製に難渋し、達成できなかった。補助金による研究終了後もさらなる工夫を行って継続したい。並行する研究では、各種GISTの病態の解明や実臨床での再発高リスクGIST症例の実態等が明らかにでき、今後のGIST診療に役立つものと考えられた。