Improvement of conventional adoptive cell therapy for cancer utilized tumor-specific immune responses induced by radiation therapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07790
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Institutes for Quantum Science and Technology
• Principal Investigator: Takeshima Tsuguhide 国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 重粒子線治療研究部, 主幹研究員 (10360950)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 放射線治療 / 免疫治療 / 樹状細胞 / がん結合抗体 / がん反応性CTL

Outline of Final Research Achievements

The purpose of this study was to create the improved dendritic cell vaccine therapy for cancer. Tumor-binding antibodies (TAbs), induced in serum after X-ray tumor irradiation, were bound to the Fc receptors on bone marrow-derived dendritic cells (BMDC). The therapeutic effects of the TAb-BMDC were compared to that of the conventional BMDC therapy.
In a murine model of melanoma (B16-OVA), no statistical difference in therapeutic efficacy was seen between TAb-BMDC therapy and conventional BMDC therapy. But when combined with X-ray therapy, the TAb-BMDC was more effective than conventional BMDC in inhibiting tumor growth by augmenting the induction of antitumor cellular immune responses. This multimodality regimen may have translational applications for the treatment of human cancers.

Free Research Field

腫瘍免疫学、放射線生物学

Academic Significance and Societal Importance of the Research Achievements

近年の放射線照射技術の向上に伴い、腫瘍の原発巣の制御はある程度可能になったものの、多くの癌種で見られる遠隔転移巣や播種を消失させることは未だに困難であり、放射線治療を受けた患者の主な死因がそれらである。本研究は、放射線治療の効果を向上させ上記問題点を克服するために、治療後に引き起こるがん特異的免疫応答をより高めることを動物モデルを使って目指した。放射線療法に免疫療法（樹状細胞ワクチン療法）を併用することに加え、放射線治療後に血中にできるがん結合抗体を取り出して樹状細胞に結合させ、それを樹状細胞ワクチン療法に使用するというこの治療法の改良版を開発した。