Interferon-beta gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice.
Despite the potential of type 1 interferons (IFNs) for the treatment of cancer, clinical experience with IFN protein therapy of solid tumors has been disappointing. IFN-beta has potent antiproliferative activity against most human tumor cells in vitro in addition to its known immunomodulatory activities. The antiproliferative effect, however, relies on IFN-beta concentrations that cannot be achieved by parenteral protein administration because of rapid protein clearance and systemic toxicities. We demonstrate here that ex vivo IFN-beta gene transduction by a replication-defective adenovirus in as few as 1% of implanted cells blocked tumor formation. Direct in vivo IFN-beta gene delivery into established tumors generated high local concentrations of IFN-beta, inhibited tumor growth, and in many cases caused complete tumor regression. Because the mice were immune-deficient, it is likely that the anti-tumor effect was primarily through direct inhibition of tumor cell proliferation and survival. Based on these studies, we argue that local IFN-beta gene therapy with replication-defective adenoviral vectors might be an effective treatment for some solid tumors.
Qin
X Q
XQ
Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA. xiao-qiang_qin@biogen.com
Tao
N
N
Dergay
A
A
Moy
P
P
Fawell
S
S
Davis
A
A
Wilson
J M
JM
Barsoum
J
J
D000256:Adenoviridae; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D003110:Colonic Neoplasms; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008113:Liver Neoplasms; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D011994:Recombinant Proteins; D016899:Interferon-beta; D001616:beta-Galactosidase