Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2

被引:7
作者
Borrione, P [1 ]
Montacchini, L [1 ]
Beggiato, E [1 ]
Pileri, A [1 ]
Bianchi, A [1 ]
Massaia, M [1 ]
机构
[1] UNIV TURIN,OSPED MOLINETTE,DIPARTIMENTO MED & ONCOL SPERIMENTALE,DIV EMATOL,I-10126 TURIN,ITALY
关键词
OKT3; IL-2; immunotheraphy; anti-CD3; advanced cancer; myeloma; lymphoma; melanoma;
D O I
10.3109/10428199209067615
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 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-CDS mAb (OKT3) followed by continuos 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.
引用
收藏
页码:325 / 330
页数:6
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