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Abstract
Background. Cytotoxic T lymphocytes (CTL) have been shown to be useful for adoptive immunotherapy
in malignancy. Traditional sources for CTL, such as tumor-infiltrating lymphocytes,
have limitations. It would therefore be useful to develop a method of generating antitumor
CTL from a renewable source such as peripheral blood.
Methods. DBA/2 mice were injected intradermally in the abdominal wall with the murine tumor
PHS-5 and killed 14 days later. Peripheral blood lymphocytes were harvested and cultured
with 20 units/ml interleukin-2 and autologous tumor-stimulator cells treated with
mitomycin C. Cultures were split when greater than 2 × 106 cells/well, fed every 3 days and stimulated weekly.
Results. Lymphocytes expanded greater than 130,000-fold during 8 weeks. Specific cytotoxicity
was shown with 51Cr release assay. Withdrawal of repeated stimulation with autologous tumor resulted
in failure of cells to expand in culture and loss of cytotoxicity. In vivo administration
showed marked reduction of 10-day liver metastases, indicating therapeutic efficacy.
Conclusions. These data demonstrate a successful animal model of adoptive immunotherapy with CTL
generated from peripheral blood lymphocytes.
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Article info
Publication history
Accepted:
February 1,
1992
Footnotes
☆Supported by the Alberta Cancer Board.
Identification
Copyright
© 1993 Published by Elsevier Inc.