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Induction of a CD3+/CD56+ lymphocyte population following gene therapy with transgenic IL-2 secreting fibroblasts in
B C Engel1, H J Laws, B Buttlies
1Department of Pediatric Hematology/Oncology, Heinrich Heine University, Düsseldorf, Germany.
Background:
Adjuvant interleukin-2 (IL-2) therapy after stem cell transplantation can improve the prognosis of patients with Ewing tumors. This has been attributed to stimulation of the immune system and its antineoplastic activity, thus eliminating minimal residual disease. As the 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 genetically modified to secrete IL-2 and then be injected to generate tumor immunogen.
Procedure:
In a preliminary clinical trial we assessed whether the administration of transgenic IL-2-secreting fibroblasts was feasible without major toxicity and whether it had any effect regarding the activation of the immune system. We treated an 11-year-old boy with a peripheral neuroectodermal tumor of the left neck in fourth relapse, who was refractory to all available therapy. We transfected fibroblasts of the patient with an IL-2 gene expression vector using a cationic liposome reagent. In 51Cr cytotoxicity assays we obtained lysis of this patient's tumor cells by IL-2-stimulated mononuclear cells (MNCs). Under CT-guidance we intratumorally injected IL-2 transgenic autologous fibroblasts.
Results:
We observed no local or systemic toxicity. In addition, we found a rise in the CD3+CD56+ lymphocyte population, previously described as cytokine-induced killer cells. No other hematological parameter changed significantly.
Conclusions:
Our data suggest that the intratumoral injection of transgenic IL-2-secreting fibroblasts is feasible without major toxicity and may lead to an increase in CD3+CD56+ cells.