Induction of autologous tumor-specific cytotoxic T cells in patients with liver cancer. Characterizations and clinical utilization.
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 nonresected 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).
Department of Surgery, Tokyo Women's Medical College, Japan.
A
A
Aruga
K
K
Yamauchi
K
K
Takasaki
T
T
Furukawa
F
F
Hanyu
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007116:Immunization, Passive; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D008114:Liver Neoplasms, Experimental / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell