REGRESSION OF HUMAN BREAST-CANCER XENOGRAFTS IN RESPONSE TO INTRALESIONAL TREATMENT WITH INTERFERON-ALPHA AND INTERFERON-GAMMA POTENTIATED BY TUMOR-NECROSIS-FACTOR

The potentiating effects of human recombinant tumor necrosis factor-al pha (rTNF-alpha) on the antitumor actions of recombinant interferon-ga mma (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 o r in combination in one of the two tumors of each mouse to study local effects while the opposite tumor was left undisturbed to evaluate sys temic effects, The tumors received 20 intralesional injections (four c ycles 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 regressions of 9 of 9 tumors with rTNF-alpha used at the dose of 5 mu g per injec tion, of 6 of 8 turners at the dose of 2.5 mu g, and of 4 of 8 tumors at the dose of 0.5 mu g. Mostly mild to moderate partial responses wer e seen in the other groups, The systemic effects on the contralateral tumors were significantly less than the local effects on the correspon ding tumors. Histologically, responding tumors showed reactive fibrosi s and inflammatory cell infiltration, No vascular alterations were see n, presumably because of the immunodeficiency of nude mice, It was con cluded that the potentiation of the antitumor actions of IFNs by rTNF- alpha was effective at the local but not at the systemic level.