Therapy of 4T1 breast cancer in mice with Vaccinia virus encoding tumor-associated antigen epitopes and mouse IL2 cytokine

Mingyu Ye^*Ivan PetrovIvaylo gentschevEman M. Othman^*Aladar A. Szalay^*

• Biocenter, University of Wuerzburg, Würzburg, Germany

Oncolytic vaccinia virus (VACV) strains are being investigated for use in immunotherapy as a new experimental cancer treatment. Here, we describe the construction, characterization, and use of VACV strains coexpressing murine Interleukin 2 (mIL2) and tumor-associated antigen (TAA)-derived epitopes as potential therapeutic agents against murine mammary carcinoma. In the 4T1 mouse mammary tumor model, VACVencoded mIL2 expression remarkably increased CD4+ and antigen-specific CD8+ T cell populations. In addition, the virus-expressed epitopes elicited an antigen-specific T cell response resulting in the inhibition of tumor cell growth. Furthermore, experiments with 4T1 tumor-bearing syngeneic BALB/c mice showed that the mIL2 and TAA-derived epitopes expressing VACV strain achieved a significantly better anti-tumoral response than the VACV strains expressing mIL2 alone. Taken together, the combination of concomitant expressions of both compounds is significantly more potent in inhibiting tumor growth than immunotherapy with IL2 alone. These findings suggest that the engineering of novel VACV strains co-expressing IL2 with peptides from tumor-associated antigen epitopes could be a novel strategy for cancer therapy in the future.