Newly Characterized Murine Undifferentiated Sarcoma Models Sensitive to Virotherapy with Oncolytic HSV-1 M002

摘要: Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity current treatments. New targeted therapies less toxicity, such as those that harness the immune system, immunocompetent murine sarcoma models to test these greatly needed. We characterized two new serendipitous of undifferentiated (SARC-28 SARC-45) tested their sensitivity virotherapy oncolytic herpes simplex virus 1 (HSV-1). Both expressed high levels primary HSV entry molecule nectin-1 (CD111) were susceptible killing by interleukin-12 (IL-12) producing HSV-1 M002 in vitro in vivo. resulted a significant intratumoral increase effector CD4+ CD8+ T cells activated monocytes, decrease myeloid-derived suppressor cells (MDSCs) mice. Compared parent R3659 (no IL-12 production), higher CD8:MDSC CD8:T regulatory cell (Treg) ratios, suggesting creates more favorable tumor microenvironment. These data provide support clinical trials targeting HSV-1. an exciting opportunity explore combination rely on intact system reach full therapeutic potential.