Lymphokine-activated killer cells from normal and lymphoma subjects are cytotoxic for cells coated with antibody derivatives displaying human Fc gamma.
Lymphokine-activated killer (LAK) cells were successfully generated in all cases from blood mononuclear cells obtained from six patients with lymphoma. The LAK cells from three of these patients and from five normal adult donors were tested for their effector abilities in antibody-dependent cellular cytotoxicity (ADCC) against guinea pig leukemic lymphocytes coated with various antiidiotype antibodies. Cells from all the donors behaved similarly. Mouse monoclonal antibodies of IgG1, IgG2a, and IgG2b isotypes invoked no ADCC. However, substantial ADCC was invoked by the chimeric antibody FabFc, in which Fab'gamma from mouse antiidiotype is thioether-bonded to human normal Fc gamma. Similar results were obtained on testing LAK cells from a normal donor against uncultured human lymphoma targets coated with native or chimeric antiidiotype. The ADCC invoked by the mouse-human chimeric antibodies appears to depend on the human Fc gamma they display and not on the univalency of the derivatives used. The findings imply that LAK technology could usefully augment serotherapy that uses antibody derivatives displaying human Fc gamma.
Dearman
R J
RJ
Tenovus Laboratory, General Hospital, Southampton, UK.
Stevenson
F K
FK
Wrightham
M
M
Hamblin
T J
TJ
Glennie
M J
MJ
Stevenson
G T
GT
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG