Activated lymph node T cells for systemic adoptive immunotherapy of malignant glioma

Abstract

Ten patients with progressive primary or recurrent malignant glioma received systemic adoptive immunotherapy to determine the feasibility, toxicity, and potential therapeutic benefits of this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. A rich source of tumor-immune T cells are lymph nodes (LNs) draining the tumor vaccine site. In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 X 108 to 1.5 X 1011. There were no Grade 3 or 4 toxicities associated with the treatment. Following T cell transfer therapy, radiographic regression that lasted at least 4 months was demonstrated in three patients with recurrent tumors, and four patients remain alive more than 11 months after surgery. The remaining patients had progressive disease, and three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer. These findings demonstrate that adoptive immunotherapy can be administered in patients with glioma without causing significant toxicity. It appears that this experimental regimen can provide therapeutic benefits for some patients.