Immune changes in peripheral blood resulting from locally directed interleukin-2 therapy in squamous cell carcinoma of the head and neck.
Interleukin-2 (IL-2) was administered locally by constant intra-arterial infusion in four escalating doses from 3 x 10(4)-3 x 10(7) IU/day to 12 patients with squamous cell carcinoma of the head and neck (SCCHN) in a phase I trial. Lymphocyte phenotypic markers and serum cytokine concentrations were measured over the course of treatment. Serum IL-1-alpha, -beta and IL-6 were not induced at any dose level. Tumour necrosis factor (TNF)-alpha was induced in the 2 patients who showed a clinical response (at the lowest dose) as well as in 4/10 of the non-responders. In addition TNF-beta was induced in 3/10 and IFN-gamma in 5/10 non-responders. Soluble IL-2 receptor concentrations were increased at the two higher doses. The highest dose of IL-2 produced a lymphocytosis after day 5 until the end of administration reflected by a general rise in lymphocyte phenotypic markers. CD25, CD3/HLA-DR and CD56 showed an additional upregulation not accounted for by the lymphocytosis with a suggestion of a bell-shaped dose-response curve for CD25 and CD3/HLA-DR. Administration of IL-2 in this manner has been shown to be well tolerated and has some anti-tumour activity at low doses, with little toxicity.
Dadian
G
G
Department of Immunology, Westminster Hospital, London, UK.
Riches
P G
PG
Henderson
D C
DC
MacLennan
K
K
Lorentzos
A
A
Moore
J
J
Hobbs
J R
JR
Gore
M E
ME
D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood*; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016130:Immunophenotyping; D016233:Immunotherapy, Active / Q000379:methods*; D007261:Infusions, Intra-Arterial; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D017252:CD3 Complex; D016207:Cytokines; D006684:HLA-DR Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma