PHASE I TRIAL OF IMMUNOMODULATORY ACTIVITIES OF HUMAN LEUKOCYTE INTERFERON IN ADVANCED CANCER PATIENTS

Publisher Summary This chapter discusses the phase I trial of immunomodulatory activities of human leukocyte interferon in advanced cancer patients. In a study described in the chapter, twenty-two patients with advanced malignancy were treated in a phase I trial of (Meloy) human leukocyte interferon (IFN-α). 40 ml of venous blood were collected in heparinized vacutainers, washed, diluted, and layered on Ficoll–Hypaque gradients to obtain the mononuclear fraction. Mononuclear cells suspended in RPMI+20% fetal calf serum (1–2 × 10 6 /ml) were layered onto plastic tissue culture flasks previously coated with murine sarcoma line TU5 microexudate. After 45 min of incubation at 37°C, nonadherent cells were decanted and further eluted with 5× washing and resuspension in RPMI+10% FCS. Nonadherent cells were counted and used as effector cells in natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) assays. Adherent cells were eluted from microexudate coated flasks by 10 min incubation in 10mM EDTA in PBS. These were washed, counted, and used as effector cells in the monocyte-mediated cytotoxicity (MMC) assay. Collected cells were 90% viable, 90% latex positive, and 90% nonspecific esterase positive. The results of this study suggested that a single dose of IFN between 10–40 × 10 6 IU/M 2 results in enhancement of natural cytolysis in as many as half of patients.