Large scale production of human lymphokine activated killer cells for use in adoptive immunotherapy

Linda Mesler Muul, Elaine P. Director, Cornelia L. Hyatt, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Immunotherapy utilizing the adoptive transfer of lymphokine activated killer (LAK) cells in conjunction with recombinant interleukin 2 (RIL-2) is capable of reducing established metastatic cancer in a variety of animal tumor models. A major difficulty in the application of these efforts to the treatment of human cancer has been the activation in vitro of up to 2 × 1011 human peripheral blood lymphocytes obtained by repeated leukaphereses. We have thus developed optimal and simplified techniques for the generation of human LAK cells for use in clinical trials. We have found that 1.5 × 109 lymphocytes separated on Ficoll-Hypaque gradients and incubated in 1000 ml of culture medium in a 2.3 liter roller bottle with 1000-1500 U of RIL-2 per ml, generated LAK cells capable of killing fresh human tumor cells in a 4 h chromium release assay. The culture medium used was RPMI 1640 with 2 mM glutamine, 2% heat-inactivated human AB serum, 50 μg/ml streptomycin and gentamicin and 50 U/ml penicillin. This technique allows activation of sufficient numbers of cells in a research laboratory setting to conduct human clinical trials. The administration of LAK cells generated in this fashion can mediate the regression of human tumors when administered in conjunction with IL-2.

Original languageEnglish (US)
Pages (from-to)265-275
Number of pages11
JournalJournal of Immunological Methods
Issue number2
StatePublished - Apr 17 1986


  • Adoptive immunotherapy
  • Human cytotoxic lymphocytes
  • Recombinant interleukin 2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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