[Transfer of interleukin 2-activated lymphocytes].
IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. We have undertaken fundamental experiments and a clinical pilot study in order to search for an efficient way of applying this therapy. Characterization of LAK cells: Human peripheral blood lymphocytes were fractionated by Ficoll-Isopaque and Percoll gradient centrifugation. The main activity was located in the low-density fraction (less than 1.061 g/ml), which corresponded to the LGL/NK fraction. However, the behavior of LAK cells against metabolic inhibitors such as DMSO, NDGA, EtOH and NaN3 was quite different from that of NK cells. LAK cells are resistant to lipoxygenation inhibitors and are labile to mitochondrial oxidation inhibitor, opposite to the behavior of NK. All the fractions sorted by FACS using CD16 and CD3 expressed LAK activity. This phenomenon was missed because LAK cells are sensitive to NaN3 which is usually contained in buffers of MoAb and in the running solution of cell sorter. Simulation study: The side effects and efficacy of LAK transfer were evaluated using Meth A sarcoma cell-bearing BALB/c mice. No side effects were observed and significant efficacy was obtained in mice whose tumors were located in the lung or abdominal cavity. Human pilot study: The pilot study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration.
D000328:Adult; D000368:Aged; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005354:Fibrosarcoma / Q000628:therapy; D006801:Humans; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000637:transplantation*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D012513:Sarcoma, Experimental / Q000628:therapy
D007376:Interleukin-2; D000431:Ethanol; D009637:Masoprocol; D004121:Dimethyl Sulfoxide