探索溶瘤病毒疗法靶向骨肉瘤

Osteosarcoma (OS) is a highly aggressive and metastatic bone malignancy that primarily affects children and young adults. Despite advances in multidisciplinary treatment, including surgery, chemotherapy, and radiation therapy, the survival rates for patients with OS have not improved significantly over the past 20 years, especially for those with metastatic disease. We hypothesize that combining cancer immunotherapies will have better therapeutic potential for osteosarcoma. We have successfully combined two immunotherapeutic modalities by developing armed canine conditionally replicative adenoviruses (CAV2-AU-M3). CAV2-AU-M3 is armed with an immune checkpoint inhibitor, an antibody to PD-1 that is released into the tumor microenvironment (TME) upon lysis. We have evaluated the oncolytic activity and production/ secretion of anti-PD1 Ab by CAV2-AU-M3 in four canine OS cell lines, D17-GLP, CF11-GLL, D22-GLP, and MCKOS in 2D and 3D cultures. We have also assayed the production and secretion of anti-PD1 Ab in cell culture media, which binds to the PD1 receptor and plays a role in inhibiting PD1-PDL1 binding. CAV2-AU-M3 represents a next-gen approach to immunotherapies in solid tumors and creates a blueprint to guide the development of similar treatments in solid tumors such as osteosarcoma.