Exploration of molecular mechanism and therapeutic application of humoral tumor immunity based on sulfated-glycosaminoglycan antigens and immunogenomics

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H01032
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Katoh Hiroto 東京大学, 大学院医学系研究科(医学部), 准教授 (60446549)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 液性腫瘍免疫 / 免疫レパトア / がん治療抗体 / 硫酸化糖鎖

Outline of Final Research Achievements

Aiming to elucidate the essential role of humoral immunity in the tumor microenvironment, I utilized single-cell immune repertoire sequencing across various clinical cancer samples, isolating numerous cancer-specific antibodies and beginning to unravel novel molecular mechanisms of humoral tumor immunity. Additionally, I identified that the antigens recognized by the tumor-specific antibodies which I had identified from human cancer environments were "densely-sulfated glycosaminoglycans." Further experiments using a mouse xenograft model demonstrated that such anti-densely-sulfated glycosaminoglycan antibodies exhibited clear anti-tumor effects against multiple cancers, revealing their potential applicability as therapeutic antibodies.

Free Research Field

ゲノム病理学

Academic Significance and Societal Importance of the Research Achievements

本研究は、がんの手術検体に対して新しい技術を応用した詳細な解析を行うことで、がん細胞を認識する新しい抗体を発見することを一つの目的としており、本研究の成果によってその一部が達成されたといえる。また、本研究によって得られたデータによって、がん組織で起こっている免疫現象についての理解を一段と深めることができ、将来的に新しいがん治療として応用していくことが可能な発見を多く得ることができた。