In an aggressive B16-F10 murine
melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic
vaccine (
Vx) composed of B16-F10
cell extracts and lipoplexes carrying the genes of human
interleukin-2 and murine granulocyte and
macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with
Vx was able to slow down the fast evolution of this
tumor. After surgery, both SG and SG +
Vx treatments, significantly prevented (in 50% of mice) or delayed (in the remaining 50%) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG +
Vx) and overall median survival (SG +
Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the
tumor from surrounding host tissue. Both, SG and the subcutaneous
Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of the SG +
Vx group suggested the development of an effective systemic immunostimulation that enhanced (18)FDG accrual in the thymus, spleen and vertebral column. When combined with surgery, direct
intralesional injection of suicide gene plus distal subcutaneous genetic
vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes.