Regression of human breast cancer xenografts in response to intralesional treatment with interferons alpha and gamma potentiated by tumor necrosis factor.
The potentiating effects of human recombinant tumor necrosis factor-alpha (rTNF-alpha) on the antitumor actions of recombinant interferon-gamma (rIFN-gamma) and of natural interferons alpha and gamma combined (nIFN-alpha/nIFN-gamma) were studied on human breast cancer xenografts growing bilaterally in nude mice. The cytokines were injected singly or in combination in one of the two tumors of each mouse to study local effects while the opposite tumor was left undisturbed to evaluate systemic effects. The tumors received 20 intralesional injections (four cycles of 5 daily injections each). In injected tumors the best results were obtained with nIFN-alpha/nIFN-gamma supplemented with rTNF-alpha. The responses were dose dependent, resulting in complete regression of 9 of 9 tumors with rTNF-alpha used at the dose of 5 micrograms per injection, of 6 of 8 tumors at the dose of 2.5 micrograms, and of 4 of 8 tumors at the dose of 0.5 microgram. Mostly mild to moderate partial responses were seen in the other groups. The systemic effects on the contralateral tumors were significantly less than the local effects on the corresponding tumors. Histologically, responding tumors showed reactive fibrosis and inflammatory cell infiltration. No vascular alterations were seen, presumably because of the immunodeficiency of nude mice. It was concluded that the potentiation of the antitumor actions of IFNs by rTNF-alpha was effective at the local but not at the systemic level.
Ozzello
L
L
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
de Rosa
C M
CM
Cantell
K
K
Kauppinen
H L
HL
Habif
D V
DV
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D013045:Species Specificity; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma