Synergism between alpha-interferon and interleukin-2-activated killer cells: in vitro studies.
The effects of a combination of recombinant alpha-interferon (IFN-alpha) 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-alpha for at least 1 day increased their susceptibility to the lytic activity of LAK cells. The combination of the two agents in sequence (IFN-alpha followed by LAK cells) resulted in a true synergystic killing of both IFN-alpha-sensitive and resistant tumor cells. No synergy was observed when the sequence was reversed (LAK cells followed by IFN-alpha). When peripheral blood mononuclear cells were incubated simultaneously with IFN-alpha 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.
D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008545:Melanoma; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins