Intraperitoneal lymphokine-activated killer cell/interleukin-2 therapy in patients with intra-abdominal cancer: immunologic considerations.
Lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2) were administered by the ip route to patients with intra-abdominal malignancies. Pharmacokinetic studies of IL-2 revealed 10- to 100-fold higher concentrations of IL-2 in peritoneal fluid versus serum. Ip levels of IL-2 were maintained well above those required to generate and maintain LAK cells in vitro. LAK cell activity was detectable in the peritoneal fluid for the duration of each treatment cycle and did not disappear until IL-2 was discontinued. Detection of interferon-gamma (IFN-gamma) in the peritoneal fluid of all patients was consistent with production in situ by activated lymphocytes. In some patients, low but detectable levels of IFN-gamma were also found in the serum. In vivo activation of monocytes in the peritoneal fluid as measured by in vitro production of hydrogen peroxide was documented in the majority of patients. Neither interleukin-1 nor tumor necrosis factor-alpha was detected in the peritoneal fluid. We found no correlation between the presence or levels of IL-2, IFN-gamma, or LAK cell lytic activity in peritoneal fluid or serum and response or nonresponse to therapy.
Urba
W J
WJ
Program Resources, Inc., National Cancer Institute, Frederick Cancer Research Facility, MD 21701.
Clark
J W
JW
Steis
R G
RG
Bookman
M A
MA
Smith
J W
JW
Beckner
S
S
Maluish
A E
AE
Rossio
J L
JL
Rager
H
H
Ortaldo
J R
JR
D000008:Abdominal Neoplasms / Q000276:immunology / Q000628:therapy*; D001202:Ascitic Fluid / Q000276:immunology; D006801:Humans; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000378:metabolism; D011237:Predictive Value of Tests; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma