In vivo induction of the lymphokine-activated killer phenomenon: interleukin 2-dependent human non-major histocompatibility complex-restricted cytotoxicity generated in vivo during administration of human recombinant interleukin 2.
The availability of purified human recombinant interleukin 2 (IL-2) has enabled clinical trials to test its in vivo effects. We report here the immunological effects of 7 consecutive days of IL-2 treatment given to 25 patients with cancer in a clinical Phase I study. Peripheral blood lymphocytes obtained from patients following therapy with IL-2 had enhanced proliferative responses to IL-2 and enhanced direct cytotoxic activity on K562 target cells. This lytic activity was further augmented by the addition of IL-2 during the 51Cr release assay. Fresh peripheral blood lymphocytes from some patients who had just completed treatment at the higher IL-2 dose levels were able to kill both the natural killer-resistant Daudi cell line and fresh tumor cells while pretreatment samples and peripheral blood lymphocytes from healthy controls were not. This lytic activity was best detected when IL-2 was present in the in vitro effector assay. These results demonstrate that the administration of IL-2 to patients with cancer induces a population of effector cells able to directly destroy natural killer-resistant target cells, when assayed in the presence of IL-2.
Hank
J A
JA
Department of Human Oncology, University of Wisconsin, Madison 53792.
Kohler
P C
PC
Weil-Hillman
G
G
Rosenthal
N
N
Moore
K H
KH
Storer
B
B
Minkoff
D
D
Bradshaw
J
J
Bechhofer
R
R
Sondel
P M
PM
D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D007113:Immunity, Innate; D007167:Immunotherapy; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage
D007376:Interleukin-2; D011994:Recombinant Proteins