Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial.
Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.
Ernstoff
M S
MS
Department of Medicine, University of Pittsburgh, School of Medicine, Pennsylvania.
Gooding
W
W
Nair
S
S
Bahnson
R R
RR
Miketic
L M
LM
Banner
B
B
Day
R
R
Whiteside
T
T
Titus-Ernstoff
L
L
Kirkwood
J M
JM
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007694:Killer Cells, Natural / Q000276:immunology; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase