Intratumoral administration of a recombinant canarypox virus expressing interleukin 12 in patients with metastatic melanoma

Academic Article

Abstract

  • The aim of this study was to evaluate the tolerability and activity of intratumoral administered human interleukin 12 encoded by a vector derived from the canarypox virus (ALVAC-IL-12). Nine patients with surgically incurable metastatic melanoma who had subcutaneous nodules available for injection were enrolled. ALVAC-IL-12 was administered by intratumoral injection on days 1, 4, 8, and 11. Tumor nodules greater than 2 cm in diameter were injected with 2 × 106 median tissue culture infectious doses (TCID 50), and smaller tumors were injected with 1 × 106 TCID50. The total dose per patient per time point ranged from 1 × 106 to 4 × 106 TCID50. Toxicity was mild to moderate and consisted of inflammatory reactions at the injection site and fever associated with chills, myalgia, and fatigue. No dose-limiting toxicities occurred. Increases in IL-12 mRNA, and also increases in interferon γ mRNA, were observed in ALVAC-IL-12-injected tumors compared with saline-injected control tumors in four of the nine patients. ALVAC-IL-12-injected tumors were also characterized by T cell infiltration. Three patients demonstrated increases in serum IL-12 and in interferon γ levels. All patients developed neutralizing IgG antibody to the canarypox vector. One patient manifested a complete response of injected subcutaneous metastases and uninjected in-transit metastases. The intratumoral injection of ALVAC-IL-12 at these dose levels and according to this schedule was well tolerated and resulted in measurable biologic response in patients with metastatic melanoma.
  • Published In

  • Human Gene Therapy  Journal
  • Digital Object Identifier (doi)

    Author List

  • Triozzi PL; Strong TV; Bucy RP; Allen KO; Carlisle RR; Moore SE; LoBuglio AF; Conry RM
  • Start Page

  • 91
  • End Page

  • 100
  • Volume

  • 16
  • Issue

  • 1