Investigation of target molecules involved in tumor lymphangiogenesis and their development towards cellular therapy.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16841
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kitasato University
• Principal Investigator: MAEHANA Shotaro 北里大学, 医療衛生学部, 講師 (40803177)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 欠損ウイルスベクター / 細胞療法

Outline of Final Research Achievements

The investigators conducted an exploration of comprehensive molecular components for controlling the cancer microenvironment and suppressing metastasis by applying a genetically modified cell therapy that they have independently developed, targeting the tumor lymphatic environment. Initially, therapeutic cells and tumor cell lines were established using retroviral vectors to produce high levels of sVEGFR-3 protein. Using these established cells, the effects on tumor cells in an extracellular environment and the evaluation and comprehensive analysis of lymphatic metastasis in mouse models were performed. The results suggested the importance of matrix metalloproteinases, which metabolize the extracellular matrix, growth factors, and chemokines in the tumor lymphatic environment. These findings indicated the potential of matrix metalloproteinases as novel therapeutic candidates, and therefore, the application of this knowledge to new cell therapies in the future is worth considering.

Free Research Field

細胞療法

Academic Significance and Societal Importance of the Research Achievements

がん患者の治療においては、外科手術や薬物治療などの直接的にアプローチする本体的治療とともに、がん治療において発生する副作用を軽減する支持療法が不可欠であり、全身投与による血小板減少・顆粒球減少・骨髄抑制など様々な副作用が生じる患者への負担を軽減する治療法が望ませれる。本研究の細胞治療では、がん組織局所において薬剤濃度を高め、血中の治療物質濃度を高めないメリットがある。本研究により肺組織と周囲リンパ節への転移に関わるVEGF-Cの役割と新たな治療候補分子を解析することができたことから、がん患者の治療による負担軽減へつながる治療法の開発へとつながることを期待する。