Lymphokine-activated killer cells: in vitro and in vivo studies

The unavailability in humans of the specifically sensitized syngeneic cells that have proven efficacy in mouse tumor models has led us to adopt alternative approaches for the generation of cells reactive with fresh human tumor. We have demonstrated that incubation in lectins, alloantigens, or interleukin 2 for only 3 days can generate cells highly lytic for fresh NK-resistant primary and metastatic tumor but not normal cells. The effector cells are OKT3+, OKT8+, and the precursors appear to be distinct from NK and T cells. In murine models, the adoptive transfer of these activated cells leads to a marked reduction in established lung metastases and prolongation of the survival time, especially when combined with infusions of interleukin 2. We have performed a phase I clinical trial using infusion of large numbers of lectin-activated cells. No major toxicity was found, and circulating activated cells with evidence of migration to tumor were achieved. No major clinical responses occurred in these patients with very large tumor burdens. Clinical trials using the combined administration of interleukin 2-activated cells and recombinant interleukin 2 are in progress.