Murine interferon-alpha1 gene-transduced ESb tumor cells are rejected by host-mediated mechanisms despite resistance of the parental tumor to interferon-alpha/beta therapy.
The highly metastatic ESb tumor is totally resistant to murine interferon-alpha/beta (IFN-alpha/beta) therapy, regardless of the number of cells injected or the route of inoculation. In contrast, as we show herein, mouse IFN-alpha1-transduced ESb tumor cells were inhibited markedly when injected subcutaneously into immunocompetent mice. IFN-producing ESb tumor rejection was mediated by the immune system, because these tumor cells grew normally in immunosuppressed mice. Tumor regression was accompanied by extensive necrosis and cellular infiltrates in the tumor area. These results further support the use of IFN-alpha in cytokine gene therapy of cancer and suggest the advantage of using gene transfer rather than cytokine administration to enhance an antitumor immune response.
Rozera
C
C
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Mecchia
M
M
Gresser
I
I
Bandu
M T
MT
Proietti
E
E
Venditti
M
M
Sestili
P
P
Santini
S M
SM
Fais
S
S
Belardelli
F
F
Ferrantini
M
M
D000818:Animals; D018432:Drug Resistance, Multiple; D018014:Gene Transfer Techniques; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000235:genetics*; D016899:Interferon-beta / Q000008:administration & dosage / Q000235:genetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D016899:Interferon-beta