Tumor-Specific Oncolytic Adenovirus Breaks Through Immunotherapy Resistance in Bone and Soft Tissue Sarcomas

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22814
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Okayama University
• Principal Investigator: KURE MIHO 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (30884647)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 腫瘍融解アデノウイルス / 抗PD-1抗体 / 骨肉腫

Outline of Final Research Achievements

Cases of bone and soft tissue sarcoma that are refractory to chemotherapy or have distant metastases have a poor prognosis. Immunotherapy is attracting attention as a new treatment option, but osteosarcoma is not responsive to immunotherapy. How to enhance the effect of immune response is under investigation. Using our tumor-specific replication-competent oncolytic adenovirus OBP-702, we investigated the therapeutic effect of combination therapy with OBP-702 and anti-PD-1 antibody. First, infection of osteosarcoma cell lines with OBP-702 increased PD-L1 and PD-L2 expression, indicating that OBP-702 formed a favorable environment for immunotherapy. A high lung metastasis strain was then created. Cytokines were examined, and the possibility that metastasis could be suppressed by OBP-702 was observed. We are planning to conduct therapeutic experiments using mice.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

本研究は骨軟部腫瘍に関し、OBP-702の免疫原性細胞死誘導による免疫チェックポイント阻害剤の有効性増幅効果について検討するものであり、遠隔転移難治例に対する有効な治療法としての発展が期待される。本研究は、骨軟部肉腫において免疫療法の効果が乏しい現状を打破できる可能性のあるものであり、その他の免疫治療との併用への発展性をも秘めている。OBP-702は我々が開発したものであり、本研究開発は我々にしか行えず、臨床的に有意義な研究である。