p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death

Area of Science:

• Oncology
• Immunotherapy
• Virology

Background:

• Osteosarcoma (OS) is a primary bone cancer in children and adolescents, often resistant to immunotherapy due to a weak immune response.
• Chemotherapy and virotherapy can trigger immunogenic cell death (ICD), leading to abscopal effects in untreated tumors.

Purpose of the Study:

• To evaluate the potential of chemotherapeutic drugs and telomerase-specific oncolytic adenoviruses (OBP-301, OBP-702) to induce ICD in osteosarcoma cells.
• To compare the efficacy of OBP-702 with chemotherapy and OBP-301 in inducing ICD and antitumor immune responses.

Main Methods:

• Human (U2OS, MNNG/HOS, SaOS-2) and murine (NHOS) osteosarcoma cells were treated with doxorubicin, cisplatin, OBP-301, and OBP-702.
• Immunogenic cell death (ICD) was assessed by measuring the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1).
• Therapeutic efficacy was evaluated in subcutaneous NHOS tumor models, assessing CD8+ T cell infiltration and abscopal effects.

Main Results:

• OBP-702 induced more potent ICD, evidenced by higher ATP and HMGB1 secretion, compared to chemotherapy and OBP-301 in human OS cells.
• Murine NHOS cells showed greater sensitivity to OBP-702 than OBP-301.
• Intratumoral OBP-702 injection in mice significantly increased cytotoxic CD8+ T cell infiltration and demonstrated an abscopal effect against non-treated tumors.

Conclusions:

• OBP-702 exhibits significant potential as an antitumor agent for osteosarcoma.
• OBP-702 effectively induces ICD through ATP and HMGB1 secretion, promoting an abscopal effect.
• The findings support OBP-702 as a promising candidate for osteosarcoma immunotherapy.