Reduction of end-stage malignant glioma by injection with autologous cytotoxic T lymphocytes

Abstract

Autologous cytotoxic T lymphocytes (CTL) against primary-cultured malignant gliomas were generated from peripheral blood mononuclear cells in vitro in 4 patients. Activities of the CTL were highly specific to the corresponding autologous glioma and were inhibited, in one patient, with antibodies against CD3, CD8 and MHC-class I molecules. When the CTL were injected 3 times into the primary-tumor-resected cavity via an Ommaya tube, reduction of the recurrent tumors with magnetic resonance imaging (MRI)-measured volumes exceeding 45 cm3 was observed in 3 patients. In a patient with glioblastoma multiforme (GBM), the tumor volume (estimated, 130 cm3) was rapidly reduced to 1/3, although re-recurrence of the tumor followed 40 days later. A slight but distinct rapid reduction of the tumor volume was observed in another GBM patient and in an anaplastic astrocytoma patient; essentially no change was observed in a further GBM patient. These results suggest that adoptive immunotherapy with autologous CTL will be clinically effective against end-stage malignant gliomas.