Premium
Induction of autologous tumor‐specific cytotoxic T cells in patients with liver cancer. Characterizations and clinical utilization
Author(s) -
Aruga Atsushi,
Yamauchi Katsumi,
Takasaki Ken,
Furukawa Takaji,
Hanyu Fujio
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910490105
Subject(s) - cytotoxic t cell , ctl* , peripheral blood mononuclear cell , cd8 , medicine , cancer , in vitro , immunology , cancer research , pathology , antigen , biology , biochemistry
To generate autologous‐tumor‐specific cytotoxic T cells (CTL), peripheral blood mononuclear cells (PBMC) obtained from cancer patients were cultivated with autologous tumor cells for 5 days, and restimulated with interleukin‐2 for another 5 days. Subsequently, their cytotoxic activity was examined by an in vitro cytotoxic test as well as by Winn's assay utilizing nude mouse transplanted autologous tumors. The present results demonstrated that these in vitro ‐stimulated cells were able to kill autologous tumor cells but not allogeneic tumors, and that they also inhibited the growth of transplanted autologous tumors in the nude mouse. Their cytotoxic activity was completely abrogated by pre‐treatment with either anti‐CD3 or anti‐CD8, but not with anti‐CD4, plus complement. Based on these studies, we injected these CTL via the hepatic artery into patients having either non‐resected tumors or recurrent tumors in the liver. Among 15 treated patients (13 with hepatocellular carcinoma and 2 with metastatic liver cancer) 2 complete responses, 3 partial responses and 4 minor responses were observed. During the 6 to 25 months following injection of CTL, no definite signs of tumor recurrence or regrowth were demonstrated in these 5 responding patients (complete plus partial).