Intratumoral administration of a recombinant canarypox virus expressing interleukin 12 in patients with metastatic melanoma.
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.
Triozzi
Pierre L
PL
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294, USA. pierre.triozzi@ccc.uab.edu
Strong
Theresa V
TV
Bucy
R Pat
RP
Allen
Karen O
KO
Carlisle
Ronda R
RR
Moore
Susan E
SE
Lobuglio
Albert F
AF
Conry
Robert M
RM
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*
D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma