Potentiation of therapeutic effect of recombinant tumor necrosis factor against B16 mouse melanoma by combination with recombinant interleukin 2.

Treatment of B16 melanoma-bearing mice with recombinant tumour necrosis factor (rTNF) caused a marked inhibition of tumour growth but did not result in the complete cure of the tumour-bearing mice. In contrast, combination therapy of B16-bearing mice with r-TNF and recombinant interleukin 2 (rIL-2) potentiated the therapeutic effect of rTNF and 30% of the mice were totally cured from tumour. Spleen cells obtained from B16-bearing mice showed markedly decreased immune responses including IL-2 production, IL-2 responsiveness and mixed lymphocyte reaction owing to the existence of suppressor macrophages. However, spleen cells obtained from mice cured with rTNF plus rIL-2 showed the same level of T cell responsiveness as that from normal mice. The decreased induction of alloantigen-specific cytotoxic T lymphocytes (CTL) in B16-bearing mice was also recovered after treatment with rTNF plus rIL-2. Moreover, B16-specific CTL, which could not be induced in normal or B16-bearing mice, was effectively induced from the spleen cells of B16-cured mice by rTNF and rIL-2. These results demonstrated that local therapy of melanoma with rTNF and rIL-2 was effective and induced systemic antitumour immunity in vivo.