Identification and expansion of human lymphokine-activated killer cells: Implications for the immunotherapy of cancer

Immunotherapy with lymphokine-activated killer (LAK) cells and interleukin 2 (IL-2) has been demonstrated to cause the regression of some human tumors. Expansion of peripheral blood lymphocytes (PBL) in recombinant or naturally produced IL-2, mitogens, and feeder cells results in a progressive expansion of cell number but a decline in lytic activity with time. Lytic activity for fresh tumor is best generated in IL-2 alone from specific purified subpopulations of lymphocytes. The precursor of the LAK cell has been isolated from a nonadherent, sheep erythrocyte receptor negative (E^-) lymphocyte subpopulation by the selection of Leu 11⁺ and Leu 15⁺ cells by cell sorting. Separation resulted in a significant increase (P₂ < 0.05) in lytic activity against fresh tumor by the separated 11⁺15⁺ lymphocytes compared to the 11^-/15^- lymphocytes or PBL. Leu 11⁺/15⁺ lymphocytes could be expanded up to eightfold in IL-2 alone with maintenance of lytic activity. We identified two surface antigens on the LAK precursor cell, Leu 15 and Leu 11, and demonstrated a technique for obtaining purified populations of these cells. Purified and expanded LAK cells when administered to patients may have a role in increasing the potency and decreasing the toxicity associated with this therapy.