Lymphokine-activated killer cell plus recombinant interleukin-2 therapy of erythroleukemia in mice.
The antileukemic effects of lymphokine-activated killer (LAK) cells plus recombinant interleukin-2 (rIL-2) therapy were assessed in mice with Friend virus (FV)-induced erythroleukemia. LAK cells were generated by incubating normal spleen cells for 72 hr in the presence of rIL-2 (1000 units/ml). At the time of injection, the LAK cells were cytotoxic in vitro against FV-infected fibroblasts and NK-sensitive and -resistant tumor targets but not normal controls. To determine in vivo activity, fully leukemic mice (spleen weight greater than 0.75 g) were injected with either PBS or LAK cells (10(8) cells/mouse IV at 14 and 17 days post virus) and rIL-2 (10,000 units/mouse IP every 8 hr on days 14 through 18 post virus). More than 70% of the progressively leukemic mice experienced permanent leukemia regressions (disease-free for greater than 100 days) following LAK cell plus rIL-2 therapy. Regressions were characterized by return of spleen and liver weights to normal and elimination of virus-infected erythroid (CFU-E) and macrophage (CFU-C) progenitor cells from spleen and marrow. Leukemic animals treated with either LAK cells alone or IL-2 alone experienced only transient leukemia regressions. These results demonstrate that LAK cell plus rIL-2 treatment can induce permanent regressions in progressively leukemic mice and provide a responsive and manipulable model system to elucidate the mechanisms involved in this form of immunotherapy.
Laboratory of Experimental Hematology, AMC Cancer Research Center, Denver, CO 80214.
C S
CS
Johnson
S M
SM
Thurlow
P
P
Furmanski
D000818:Animals; D001853:Bone Marrow / Q000382:microbiology; D003602:Cytotoxicity, Immunologic; D005622:Friend murine leukemia virus; D007111:Immunity, Cellular; D007116:Immunization, Passive; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins; D013154:Spleen / Q000382:microbiology
D007376:Interleukin-2; D011994:Recombinant Proteins