To address this unmet need, we evaluated KLS-3021, a novel oncolytic vaccinia virus encoding PH-20, IL-12, and soluble PD1-Fc.<h4>Methods</h4>KLS-3021 was assessed in two orthotopic prostate cancer models: a prostate-confined model with bioluminescence-positive, non-gross tumors, and a visible/palpable locally invasive model with regional lymphatic spread. The gene discussed is SPAM1; the disease is prostate carcinoma.