Oncolytic virus with an immune stimulatory payload for osteosarcoma therapy

Area of Science:

• Oncology
• Virology
• Immunotherapy

Background:

• Osteosarcoma (OS) is an aggressive bone cancer with stagnant survival rates.
• New therapeutic strategies are urgently needed for OS treatment.

Purpose of the Study:

• To develop and evaluate an enhanced oncolytic adenovirus (CAV2-AU-M3) for osteosarcoma treatment.
• To assess the efficacy of CAV2-AU-M3, armed with an anti-PD1 heavy-chain antibody (HcAb), against canine OS cell lines and in a mouse model.

Main Methods:

• Characterization of CAV2-AU-M3 infectivity and lytic properties in canine OS cell lines (monolayer and spheroid cultures).
• Assessment of anti-PD1 Ab production by CAV2-AU-M3.
• Evaluation of intratumoral CAV2-AU-M3 administration in a mouse model.
• Analysis of anti-PD1 Ab binding to PD1 receptors and inhibition of PD-1/PD-L1 interaction.

Main Results:

• CAV2-AU-M3 demonstrated infectivity and lysis of canine OS cell lines with varying efficiencies.
• Consistent production of functional anti-PD1 Ab by CAV2-AU-M3 across all tested OS cell lines.
• The produced anti-PD1 Ab effectively bound to PD1 receptors and inhibited PD-L1 binding.

Conclusions:

• CAV2-AU-M3 is a promising oncolytic virotherapy agent for osteosarcoma.
• The dual mechanism of oncolysis and PD-1/PD-L1 blockade offers a potential new therapeutic avenue for OS.