The effects of a combination of recombinant alpha-interferon (IFN-α) and interleukin-2 (IL-2)-activated human killer cells (lymphokine-activated killer or LAK cells) on Hs294T (IFN-sensitive) and A375P (IFN-resistant) human melanoma cell lines were evaluated. Pretreatment of target cells with IFN-α for at least 1 day increased their susceptibility to the lytic activity of LAK cells. The combination of the two agents in sequence (IFN-α followed by LAK cells) resulted in a true synergystic killing of both IFN-α-sensitive and -resistant tumor cells. No synergy was observed when the sequence was reversed (LAK cells followed by IFN-α). When peripheral blood mononuclear cells were incubated simultaneously with IFN-α and IL-2, LAK cell generation and antitumor activity was markedly inhibited when tested against both IFN-treated and -non-treated tumor cells. These studies may be used to plan clinical trials of combination cytokine therapy for human cancer.
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