Poxvirus-Based Strategies for Combined Vaccine and Tumor Microenvironment Manipulation

Recombinant Poxvirus and the Tumor Microenvironment: Oncolysis, Immune Regulation and Immunization

“…Intratumoral (but not s.c.) treatment with a cocktail of rVVs encoding GM-CSF and relevant antigen-encoding genes resulted in a tumor specific systemic immune response, but was still unable to cause tumor regression [ 30 ]. Knowing that Tregs can produce IL-10 and inhibit immune responses in the TME [ 90 ], we made use of the Treg-depleting anti-CD-25 antibody PC61 to test if Treg ablation in our MB49 model would improve outcomes [ 91 ]. PC61 treatment alone had no effect on tumor growth, but PC61 synergized with our rVV treatment, improving the immune response and significantly slowing growth ( Figure 2 ).…”

“…We found that i.t. injection of a combination of VV-GMCSF and VV-neu, but not VV-GMCSF alone, induced a systemic anti-neu CD8+ T-cell response ( Figure 3 a), led to tumor regression ( Figure 3 b), and decreased splenic and TME MDSC population ( Figure 3 c) [ 91 , 92 ]. It was noted that VV-GMCSF treatment in the absence of TAA actually led to a larger MDSC population in the TME as well as systemically.…”

“…Combination treatment with the anti-CD25 monoclonal antibody PC61 and either systemic or intratumoral VV-HY (a cocktail of two rVVs encoding genes coding for two immunodominant tumor antigens) inhibits tumor growth ( a ) and results in prolonged survival ( b ) compared to treatment with either systemic or intratumoral VV-HY alone. Reprinted from [ 91 ], with permission from Elsevier.…”

“…VV-neu + VV-GMCSF + KLH) results in a tumor specific CTL response; ( b ) regression of the primary tumor; ( c ) and a decrease in systemic MDSCs, whereas systemic treatment (s.c. VV-neu + VV-GMCSF + KHL) is not effective. Reprinted from [ 91 ], with permission from Elsevier.…”