INDUCTION OR A CD3+ CD56+ LYMPHOCYTE POPULATION FOLLOWING GENE-THERAPY WITH TRANSGENIC IL-2 SECRETING FIBROBLASTS IN A CHILD WITH PERIPHERAL NEUROECTODERMAL MALIGNANCY/

Background. Adjuvant interleukin-2 (IL-2) therapy after stem cell tran splantation can improve the prognosis of patients with Ewing tumors. T his has been attributed to stimulation oi the immune system and its an tineoplastic activity, thus eliminating minimal residual disease. As t he side effects of systemic IL-2 limit the dosage, attempts have been made to locally augment the concentration of IL-2 in the proximity of the tumor. To achieve this, fibroblasts and/or tumor cells can be gene tically modified to secrete IL-2 and then be injected to generate tumo r immunogen. Procedure. In a preliminary clinical trial we assessed wh ether the administration of transgenic IL-2-secreting fibroblasts was feasible without major toxicity and whether it had any effect regardin g the activation of the immune system. We treated an 11-year-old boy w ith a peripheral neuroectodermal tumor of the left neck in fourth rela pse, who was refractory to all available therapy. We transfected fibro blasts of the patient with an IL-2 gene expression Vector using a cati onic liposome reagent. In Cr-51 cytotoxicity assays we obtained lysis of this patient's tumor cells by IL-2-stimulated mononuclear cells [MN Cs]. Under CT-guidance Lye intratumorally injected IL-2 transgenic aut ologous fibroblasts. Results. We observed no local or systemic toxicit y. In addition, we found a rise in the CD3+CD56+ lymphocyte population , previously described as cytokine-induced killer cells. No other hema tological parameter changed significantly. Conclusions. Our data sugge st that the intratumoral injection oi transgenic IL-2-secreting fibrob lasts blasts is feasible without major toxicity and may lead to an inc rease in CD3+CD56+ cells. (C) 1998 Wiley-Liss, Inc.