Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2.
CD3 engagement has been used as a surrogate for antigen-specific stimulation to trigger T cell effector functions. Exogenous IL-2 has been used to prolong and amplify CD3-induced T cell activation. Previous studies have been shown that CD3 reactivity is increased in cancer patients with preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In this study, we report 9 courses of a single infusion of anti-CD3 mAb (OKT3) followed by continuous infusion of intermediate dose IL-2 in 4 cancer patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metastatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells in the peripheral blood. An increase of lymphocytes, equally distributed between CD4+ and CD8+ subsets, was observed during treatment. Activation was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including proliferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL-2 infusions were well tolerated and no limiting toxicity was observed. The treatment did not revert tumor progression in the 2 patients with progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequential administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for treatment because of an increased number of HLA-DR+ T cells in the peripheral blood. A discrepancy was observed between the emergence of CD25+ T cells and the clinical outcome.
Borrione
P
P
Università di Torino, Dipartimento di Medicine e Oncologia Sperimentale, Ospedale Molinette, Torino, Italy.
Montacchini
L
L
Beggiato
E
E
Pileri
A
A
Bianchi
A
A
Massaia
M
M
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology*; D016516:CD4-CD8 Ratio / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D010641:Phenotype; D010976:Platelet Count / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D006684:HLA-DR Antigens; D007376:Interleukin-2