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Effects of Local Injection of ex Vivo Expanded Autologous
Tumor-specific T Lymphocytes in Cases with Recurrent Malignant Gliomas
Koji Tsuboi,
Kaoru Saijo, Eiichi Ishikawa, Hideo Tsurushima,
Shingo Takano, Yukio Morishita and Tadao Ohno
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.]. *To whom requests for reprints should be addressed, at Department
of Neurological Surgery, Institute of Clinical Medicine, University of
Tsukuba, 1-1-1 Tennohdai, Tsukuba, Ibaraki 305-8575, Japan. Phone:
81-298-53-3168/3220; Fax: 81-298-53-3214; E-mail: tsuboi@md.tsukuba.ac.jp.
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.
© 2003 American
Association for Cancer Research
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