Thiostrepton Antibody-Drug Conjugate Targeting CADM1 for Adult T-Cell Leukemia/Lymphoma Therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21113
• Project/Area Number (Other): 18H05957 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0403:Biomedical engineering and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Tanabe Aki 東京大学, 大学院工学系研究科(工学部), 特任助教 (60786367)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 抗体工学 / ファージディスプレイ / 抗体薬物複合体

Outline of Final Research Achievements

Adult T- cell leukemia /lymphoma is hematological malignancy associated with Human T-lymphotropic virus type1(HTLV-1) infection. CADM1 is cell adhesion molecule, and overexpression of CADM1 in ATLL has been reported. In this study, we attempted to develop novel anti-CADM1 antibody and Antibody-Drug Conjugate targeting ATLL cells.
We succeeded to obtain anti CADM1 antibody by phage display method, and attempted to conjugate anti-cancer drugs to anti CADM1 antibody. However, the affinity of anti CADM1 antibody was not high, and further antibody engineering was required. Crystal structurer analysis and structure-based antibody engineering was performed. Moreover, solubility of the compound was very low, and linker design was another problem to improve in the future plan.

Free Research Field

抗体工学

Academic Significance and Societal Importance of the Research Achievements

CADM1は通常のマウス免疫ではモノクローナル抗体を得ることが非常に難しく、現在モノクローナル抗体としてトリIgY抗体が研究用に用いられている。研究成果の意義として、本研究では将来的な治療薬を指向し、ヒト可変領域のフレームワークを基本骨格とする人口ファージティスプレイライブラリを用いて、通常のマウス免疫で得ることが困難であった抗CADM1抗体を取得することに成功した。