[Induction of cytotoxicity from human lymphocytes coated with bispecific antibody against human glioma cells].
A bifunctional hetero-F (ab') 2 fragment containing the Fab portions from anti-CD3 and anti-glioma monoclonal antibodies was prepared. The antibody simultaneously recognized two different molecules, the CD3 complex on effector T cells and human glioma-associated antigens on target glioma cells. This bispecific F (ab') 2 fragment induced peripheral blood lymphocytes (PBLs) from healthy donors to lyse cells of the human glioma cell line, U251MG, that is resistant to natural killer cell-mediated cytolysis. Compared with lymphokine-activated killer (LAK) activity which is obtained by exposure to interleukin (IL)-2 for more than 3 days, the maximum bispecific antibody-dependent cytotoxicity can be generated only after 24 hour exposure to IL-2. And cytotoxicity of lymphocytes triggered by the bispecific antibody was dependent upon the concentration of IL-2 in the culture medium. The effect of the bispecific antibody on LAK cells was tested in patients suffering from malignant glioma. One patient who received specific targeting therapy (LAK plus bispecific antibody) showed the disappearance of high density tumor mass from CT scan. But the patient who received only LAK therapy showed the recurrence of tumor one year after LAK treatment. These are preliminary data, but may be a promising approach in cancer immunotherapy.
Nitta
T
T
Department of Neurosurgery, Juntendo University School of Medicine.
Ishizawa
A
A
Ito
M
M
Sato
K
K
Yagita
H
H
Kumura
K
K
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007376:Interleukin-2