Inhibition of lung colonisation of a mouse mammary carcinoma by therapeutic vaccination with interferon-alpha gene-transduced tumor cells.
A spontaneously metastatic murine mammary adenocarcinoma, TSA, has been transduced with the gene for interferon alpha1 (IFN-alpha). Transfectants were used for the immunotherapy of mice bearing lung colonies induced by the intravenous inoculation of non-transduced parental cells. A significant reduction in the number of tumor colonies was obtained when repeated subcutaneous administrations of mitomycin C-blocked transfectant cells were given, commencing 3 days after an intravenous challenge with TSA cells. Intraperitoneal vaccination induced a stronger anti-tumor response than subcutaneous vaccination, and the proportion of tumor-free mice reached 50%. The potency of IFN-alpha transfectants was similar to that of IFN-gamma transfectants previously obtained from TSA. Admixture of IFN-alpha and IFN-gamma transfectant cells in the same vaccine did not increase the curative effect over that of single vaccines. In nude mice vaccination with IFN-alpha or IFN-gamma transfectants did not lead to a reduction in the number of lung colonies, indicating that an intact T cell response was required for the therapeutic effect observed in immunocompetent mice.
Rossi
I
I
Institute of Cancer Research, University of Bologna, Italy.
Nicoletti
G
G
Landuzzi
L
L
Frabetti
F
F
De Giovanni
C
C
Nanni
P
P
Musiani
P
P
Ferrantini
M
M
Belardelli
F
F
Lollini
P L
PL
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D014161:Transduction, Genetic
D019496:Cancer Vaccines; D016898:Interferon-alpha; D016685:Mitomycin; D007371:Interferon-gamma