The cytotoxic action of lymphokine activated killer cells upon the human glioma cell line U251 is stimulated by bispecific monoclonal antibody (MoAb) constructs

The ability of IL-2 stimulated mononuclear cells to kill the human glioblastoma cell line U251 has been investigated. Highest cytotoxic activity was generated in low cell density cultures incubated for 15 days with 250-1000 U/ml IL-2. Sub-optimal killing was noted, with cells only exposed to IL-2 fo...

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Bibliographic Details
Published in:Journal of neuro-oncology 1992-07, Vol.13 (3), p.203-210
Main Authors: OBUKHOV, S. K, GENNIE, M. J, TUTT, A. L, KEMSHEAD, J. T, COAKHAM, H. B, BEVERLEY, P. C
Format: Article
Language:English
Subjects:
Animal cells
Antibodies, Monoclonal - immunology
Antibody Specificity - immunology
Biological and medical sciences
Cell cultures. Hybridization. Fusion
Cytotoxicity, Immunologic - immunology
Fundamental and applied biological sciences. Psychology
Glioma - immunology
Humans
Immunoglobulin Fab Fragments - immunology
Immunoglobulin G - immunology
Killer Cells, Lymphokine-Activated - immunology
Molecular and cellular biology
Tumor Cells, Cultured
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Summary:The ability of IL-2 stimulated mononuclear cells to kill the human glioblastoma cell line U251 has been investigated. Highest cytotoxic activity was generated in low cell density cultures incubated for 15 days with 250-1000 U/ml IL-2. Sub-optimal killing was noted, with cells only exposed to IL-2 for three days. Under the latter conditions, bispecific monoclonal antibodies (MoAbs) of either anti-CD3 or anti-CD16 and an anti-NCAM MoAb stimulated LAK cell activity markedly. Anti-CD16 conjugates were found more effective than anti-CD3 and (Fab')2 constructs more efficacious than those made with whole Ig molecules. Maximal stimulation of LAK cell activity was noted with bispecific MoAbs. Little effect was observed with either single or mixtures of monomeric MoAbs. Furthermore, no effect of bispecific MoAbs was observed when target cells lacked expression of NCAM. These results could be of clinical importance as it is not always feasible to screen LAK cells for optimal activity before administration to patients. Whilst bispecific MoAbs have no effect on optimally stimulated LAK cells, they are not inhibitory and can stimulate killing under sub-optimal IL-2 stimulation.
ISSN:0167-594X
1573-7373
DOI:10.1007/BF00172471