Cytolysis of malignant glioma cells by lymphokine-activated killer cells combined with anti-CD3/antiglioma bifunctional antibody and tumor necrosis factor-alpha.
With the aim of developing an effective immunotherapy for malignant glioma, glioma cells were incubated with tumor necrosis factor-alpha (TNF-alpha) to increase their susceptibility to lysis by lymphokine-activated killer (LAK) cells. Treatment with exogenous TNF-alpha induced the expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of glioma cells. In addition, the cytolytic activity of LAK cells toward exogenous TNF-alpha treated glioma cells was significantly greater than LAK cell activity toward untreated glioma cells. This increase in cytolytic activity was blocked by anti-ICAM-1 monoclonal antibodies (MAb). Furthermore, co-treatment with a bifunctional antibody (BFA) composed of anti-CD3 (UCHT1) and antiglioma (G-22) antibodies synergistically increased the cytolytic activity of LAK cells towards TNF-alpha-treated glioma cells. These results indicate that a combination of exogenous TNF-alpha and anti-CD3/antiglioma BFA may provide an effective modified adoptive immunotherapy for patients with malignant glioma.
Yoshida
J
J
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Takaoka
T
T
Mizuno
M
M
Momota
H
H
Okada
H
H
D018033:Antibodies, Bispecific / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology* / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D005910:Glioma / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D017252:CD3 Complex; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1