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Effects of Local Injection of ex Vivo Expanded Autologous Tumor-specific T Lymphocytes in Cases with Recurrent Malignant Gliomas¹

Departments of Neurological Surgery [K. T., E. I., H. T., S. T.] and Pathology [K. S., T. O., Y. M.], Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, and RIKEN Cell Bank, RIKEN (The Institute of Physical and Chemical Research), Japan [K. S., T. O., Y. M.]

Purpose: The aim of this report was to indicate both the advantages and disadvantages of local cell transfer therapy using ex vivo expanded autologous tumor-specific T lymphocytes (ATTLs) for recurrent cases of malignant gliomas.

Experimental Design: Subjects are 10 cases of malignant gliomas consisting of 7 cases of glioblastoma multiforme, 2 cases of anaplastic astrocytoma, and 1 case of anaplastic oligoastrocytoma. All cases were recurrences. ATTLs were induced by coculturing peripheral blood mononuclear cells with autologous tumor cells in medium containing interleukin-1, -2, -4, and -6 and administered into the local tumor site in total numbers of 3–247 x 10⁷ cells. As end points, tumor response and survival time were analyzed observing clinical state.

Results: Five cases responded to this therapy (namely, one case showed complete remission, and four cases had a partial response). There were three cases of no change, and two cases of progressive disease. The overall tumor response rate was 50%. No complications were noticed, except for two cases of minor local hemorrhage and eight cases of temporary fever. Nine cases died of further tumor progression, and one case died of aspiration pneumonia, and the cause-specific survival analysis indicates that the median survival time was 5 months from the initial ATTL injection.

Conclusions: The results suggest that local administration of ATTLs is effective in recurrent malignant gliomas in that it demonstrated a high benefit:risk ratio with minor side effects. Although its antitumor effect may be temporary in some advanced cases, it is highly possible that the tumor could be stabilized when conditions are optimal.

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