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Reduction of End-stage Malignant Glioma by Injection with Autologous Cytotoxic T Lymphocytes
Authors:Hideo Tsurushima  Shu Qin Liu  Koji Tuboi  Akira Matsumura  Yoshihiko Yoshii  Tadao Nose  Kaoru Saijo  Tadao Ohno
Institution:Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-0006;RIKEN Cell Bank, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba Science City, Ibaraki 305-0074
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.
Keywords:Autologous cytotoxic T lymphocytes  Malignant glioma  Brain tumor  Adoptive immunotherapy
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