title: Intratumoral administration of a recombinant canarypox virus expressing interleukin 12 in patients with metastatic melanoma.
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 x 10(6) median tissue culture infectious doses (TCID(50)), and smaller tumors were injected with 1 x 10(6) TCID(50). The total dose per patient per time point ranged from 1 x 10(6) to 4 x 10(6) TCID(50). 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 gamma 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 gamma 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.
authors.affiliation: University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294, USA. pierre.triozzi@ccc.uab.edu
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.forename: Theresa V
authors.initials: TV
authors.lastname: Strong
authors.forename: R Pat
authors.initials: RP
authors.lastname: Bucy
authors.forename: Karen O
authors.initials: KO
authors.lastname: Allen
authors.forename: Ronda R
authors.initials: RR
authors.lastname: Carlisle
authors.forename: Susan E
authors.initials: SE
authors.lastname: Moore
authors.forename: Albert F
authors.initials: AF
authors.lastname: Lobuglio
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018150:Avipoxvirus / Q000235:genetics*; D001932:Brain Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D010957:Plasmids; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma