Pseudocowpox virus, a novel vector to enhance the therapeutic efficacy of antitumor vaccination

Objective. Antitumor viral vaccines, and more particularly poxviral vaccines, represent an active field for clinical development and translational research. To improve the efficacy and treatment outcome, new viral vectors are sought, with emphasis on their abilities to stimulate innate immunity, to display tumor antigens and to induce a specific T-cell response. Methods. We screened for a new poxviral backbone with improved innate and adaptive immune stimulation using IFN-alpha secretion levels in infected PBMC cultures as selection criteria. Assessment of virus effectiveness was made in vitro and in vivo. Results. The bovine pseudocowpox virus (PCPV) stood out among several poxviruses for its ability to induce significant secretion of IFN-alpha. PCPV produced efficient activation of human monocytes and dendritic cells, degranulation of NK cells and reversed MDSC-induced T-cell suppression, without being offensive to activated T cells. A PCPV-based vaccine, encoding the HPV16 E7 protein (PCPV-E7), stimulated strong antigen-specific T-cell responses in TC1 tumor-bearing mice. Complete regression of tumors was obtained in a CD8(+) T-cell-dependent manner after intratumoral injection of PCPV-E7, followed by intravenous injection of the cancer vaccine MVA-E7. PCPV also proved active when injected repeatedly intratumorally in MC38 tumor-bearing mice, generating tumor-specific T-cell responses without encoding a specific MC38 antigen. From a translational perspective, we demonstrated that PCPV-E7 effectively stimulated IFN-gamma production by T cells from tumor-draining lymph nodes of HPV+-infected cancer patients. Conclusion. We propose PCPV as a viral vector suitable for vaccination in the field of personalised cancer vaccines, in particular for heterologous prime-boost regimens.

Automated summary

This study identifies bovine pseudocowpox virus (PCPV) as a viral vector with strong immune stimulating abilities, capable of activating immune cells and reversing tumor-induced T-cell suppression. Using PCPV encoding the HPV16 E7 protein as a vaccine, significant antigen-specific T-cell responses were induced in experimental tumor-bearing mice, resulting in complete tumor regression. From a translational perspective, PCPV-E7 effectively stimulated IFN-γ production by T cells from tumor-draining lymph nodes of HPV+-infected cancer patients.