Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma.
BACKGROUND
Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral injection of IFN-gamma retroviral vector in advanced melanoma patients.


METHODS
This was a phase I study, in which 13 patients received a single daily injection of a retroviral vector with the IFN-gamma gene for 5 consecutive days (1.5 x 10(8) colony-forming units total dose); patients subsequently underwent resection of the injected lesion to confirm DNA transduction in situ.


RESULTS
No toxicity related to the injected vector was observed. Replication competent retrovirus was not observed in any prepared samples (n = 65). IFN-gamma expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-linked immunospot assay in six samples.


CONCLUSIONS
An injection of IFN-gamma gene/retroviral vector is well tolerated. DNA transduction was demonstrated in human subjects, confirming the feasibility of the direct injection approach for the gene therapy of solid tumors. Further trials to determine optimal schedule and potential efficacy are indicated.
PRN Research, Inc., Dallas, Texas 75246, USA.
J
J
Nemunaitis
T
T
Fong
J M
JM
Robbins
G
G
Edelman
W
W
Edwards
R S
RS
Paulson
J
J
Bruce
N
N
Ognoskie
D
D
Wynne
M
M
Pike
K
K
Kowal
J
J
Merritt
D
D
Ando
D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000009:adverse effects; D006801:Humans; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012190:Retroviridae / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome; D016662:Virus Integration
D004279:DNA, Viral; D007371:Interferon-gamma