Immune modulatory oncolytic virus for osteosarcoma therapy.

Area of Science:

• Oncology
• Virology
• Immunotherapy

Background:

• Osteosarcoma (OS) is a rare but aggressive bone cancer with limited treatment advancements.
• Current therapeutic options for OS have not significantly improved patient survival rates in recent decades.
• Novel therapeutic strategies are urgently required to combat this challenging malignancy.

Purpose of the Study:

• To develop and evaluate an enhanced canine oncolytic adenovirus (CAV2-AU-M3) engineered to express an anti-PD1 heavy chain antibody (HcAb).
• To assess the efficacy of CAV2-AU-M3 against canine osteosarcoma cell lines in vitro and in vivo.
• To investigate the virus's infectivity, lytic capabilities, and anti-PD1 antibody production.

Main Methods:

• Development of CAV2-AU-M3, an oncolytic adenovirus expressing anti-PD1 HcAb.
• Characterization of viral infectivity and lytic activity in four canine OS cell lines using monolayer and spheroid cultures.
• Assessment of anti-PD1 antibody production and its functional binding to PD1 receptors.
• Evaluation of intra-tumoral CAV2-AU-M3 administration in a mouse model of osteosarcoma.

Main Results:

• CAV2-AU-M3 demonstrated infectivity and lysis of canine OS cell lines, with varying efficiencies.
• The virus consistently produced anti-PD1 antibody across all tested osteosarcoma cell lines.
• The produced anti-PD1 antibody effectively bound to PD1 receptors and inhibited PDL1 binding.
• Intra-tumoral administration in a mouse model showed an impact on tumor growth (further details pending).

Conclusions:

• CAV2-AU-M3 is a viable oncolytic adenovirus platform for osteosarcoma treatment.
• The engineered virus effectively delivers an anti-PD1 antibody, potentially enhancing anti-tumor immunity.
• This dual-action approach warrants further investigation as a novel therapeutic strategy for osteosarcoma.