Low-dose interleukin-2 in combination with interferon-alpha effectively modulates biological response in vivo.
Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-alpha, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-alpha at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-alpha was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreatment using rIL-2, rIL-2 and rIFN-alpha, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific to rIL-2.
Schneekloth
C
C
Department of Hematology and Oncology, MHH University Medical Center, Hannover, FRG.
Körfer
A
A
Hadam
M
M
Lopez Hänninen
E
E
Menzel
T
T
Schomburg
A
A
Dallmann
I
I
Kirchner
H
H
Poliwoda
H
H
Atzpodien
J
J
D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019002:CD56 Antigen; D002292:Carcinoma, Renal Cell / Q000628:therapy; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy; D007694:Killer Cells, Natural / Q000473:pathology; D007700:Kinetics; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000473:pathology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use
D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D007370:Interferon Type I; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins