Preclinical study of photoimmunotherapy for tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Okayama University
• Principal Investigator: Noma Kazuhiro 岡山大学, 大学病院, 講師 (10534761)
• Co-Investigator(Kenkyū-buntansha): 白川 靖博 岡山大学, 医学部, 客員研究員 (60379774)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Tumor microenvironment / CAFs / Esophageal cancer / Photoimmunotherapy / immunotherapy

Outline of Final Research Achievements

The efficacy of Photoimmunotherapy (PIT) utilizing Sibrotuzumab, an anti-FAP antibody targeting Cancer-Associated Fibroblasts (CAFs), was evaluated through in vitro experiments. PIT-cancer models were established by Herceptin and Cetuximab with cancer cells. The study confirmed the effectiveness of Dual-PIT in vitro, wherein simultaneous PIT was applied to both cancer cells and CAFs. Additionally, in vivo experiments were conducted using patient-derived xenografts (PDX) derived from esophageal cancer patients. The results demonstrated the efficacy of PIT with sibrotuzumab not only in vitro but also in the PDX model. Moreover, the Dual-PIT treatment approach, targeting both cancer cells and CAFs, exhibited significant anti-tumor effects.

Free Research Field

Tumor microenvironment

Academic Significance and Societal Importance of the Research Achievements

本研究においては既に臨床応用されていた抗体抗FAP抗体Sibrotuzumabを用いたPhotoimmunotherapy（PIT）の開発、並びに癌に対するPITとの同時療法の良好な治療効果を示した。さらに患者由来PDXモデルを用いたより臨床応用に近いモデルでの治療効果を示しより臨床応用での治療効果を示した。Dual-PITは一度の照射で２つの標的、特に腫瘍微小環境（TME）並びに癌細胞を治療する画期的な方法である。TMEの中心的役割を担うCAFsの治療はTMEのremodelingを行うこととなり免疫療法などと強い相乗効果が期待される。まさに全ての癌治療を大きく改善する可能性がある。