Development antibody-drug conjugate targeting glypican-1 for novel therapy of esophageal squamous cell carcinoma.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kochi University
• Principal Investigator: SERADA Satoshi 高知大学, 医学部附属病院, 特任准教授 (50463302)
• Research Collaborator: TSUJII Shigehiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗体療法 / 食道癌

Outline of Final Research Achievements

Glypican-1(GPC1) was identified as a novel cancer antigen of intractable cancer including esophageal cancer by our group. We successfully developed anti-GPC1 monoclonal antibody with high intracellular internalizing activity specific to GPC1 expressing cells (Matsuzaki S, Naka T et al., IJC 2018). We conjugated anti-GPC1 monoclonal antibody with potent tubulin polymerization inhibitor and investigated the usefulness of antibody-drug conjugate (ADC) recognizing GPC1. GPC1-ADC inhibited the growth of GPC1 positive esophageal cancer cell lines, however, failed to inhibit GPC1 knockout esophageal cancer cell lines. We successfully developed GPC1 positive esophageal cancer PDX mice. GPC1-ADC dose dependently showed anti-tumor effect to esophageal cancer PDX mice with no weight loss. Our data suggest the efficacy and safety of GPC1-ADC to esophageal cancer.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

研究代表者らのこれまでの研究によりGlypican-1を高発現する食道癌は有意に予後不良であることが確認されていた。本研究によりGlypican-1を標的とした抗体薬物複合体が食道癌モデルマウスに対して優れた有効性と安全性を示し、in vitro でGPC1発現特異的な薬効を確認したことから、進行期や再発などの難治性食道癌に対してGPC1-ADCが有効な新規治療法となり得ることが示唆された。Glypican-1を発現する食道癌以外の様々な癌に対しても有効性を示す可能性が期待される。