Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma.
Fifteen patients with tumour recurrence following radical surgical excision of malignant melanoma were treated with a combination of interferon alpha-2a (rIFN alpha-2a) and interleukin-2 (rIL-2). Immunological monitoring (performed prior to therapy and on days 7, 21, and 28, of each course of treatment) showed significant changes of several parameters after rIFN alpha-2a and rIL-2 administration. A significant increase in cells expressing CD16 (cells bearing Fc receptor), CD25 (cells bearing IL-2 receptor), and CD56 (NK cells, activated lymphocytes), as well in levels of soluble IL-2 receptor, beta 2-microglobulin and neopterin was observed. Immunological changes were closely related to the injection of the biological agent and were more relevant during the first than the second cycle of treatment. rIFN alpha-2a and rIL-2 exerted a clear synergistic activity on the same immunological parameters. No major response was seen with the present approach: four subjects showed rapid progression of decrease during the first month of therapy, while of 11 patients who completed two courses of treatment, only five were considered in stable disease. In conclusion, our results suggest that a combination of rIFN alpha-2a and rIL-2, at dosages and schedules, used in this trial, was well-tolerated and immunologically active, but was clinically ineffective in the management of advanced melanoma.
Castello
G
G
Servizio di Immunologia Clinica, Instituto Nazionale per lo Studio e la Cura dei Tumori, Naples, Italy.
Comella
P
P
Manzo
T
T
Napolitano
M
M
Parziale
A P
AP
Galati
M G
MG
Daponte
A
A
Casaretti
R
R
Celentano
E
E
Comella
G
G
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D006684:HLA-DR Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins