Combination Immunotherapy using anti-PD-1 and cytotoxic antibodies for pleural mesothelioma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17216
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: The University of Tokushima
• Principal Investigator: YONEDA Hiroto 徳島大学, 病院, 助教 (10776876)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 悪性胸膜中皮腫 / ポドプラニン

Outline of Final Research Achievements

Cell surface expression of podoplanin was confirmed in malignant pleural mesothelioma cell lines. We confirmed that Afucosylated anti-mouse podoplanin antibody has high antibody-dependent cytotoxic activity against malignant pleural mesothelioma cell lines. Combination of anti-CTLA-4 and anti-podoplanin antibodies in mice bearing malignant pleural mesothelioma cell line showed enhanced tumor suppression compared to single agent administration. Tumor tissues in the combination treatment group showed no changes in CD4 or CD8 positive T cells, but a marked increase in NK cells. The results suggest that combination therapy with anti-CTLA-4 and anti-podoplanin antibodies may be useful as a novel Combination Immunotherapy for malignant pleural mesothelioma.

Free Research Field

がん研究

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬である抗PD-1抗体および抗CTLA-4抗体が悪性胸膜中皮腫に対して本邦で承認され、優れた治療成績を認めるものの、その効果を増強する新たな複合がん免疫療法の開発が求められている。ポドプラニンは悪性胸膜中皮腫などの様々な悪性腫瘍において特異的に高発現し、腫瘍進展に深く関与する。今回の研究で抗CTLA-4抗体が抗ポドプラニン抗体と併用することで抗腫瘍効果の増強を認めた。今後ので抗CTLA-4抗体と抗ポドプラニン抗体の併用治療が悪性胸膜中皮腫に対する治療戦略となる可能性が考えられる。