Paradoxical stimulation of normal and leukemic rat hematopoiesis by monoclonal antibody to CSF-1 receptor.
We have recently developed a rat monoclonal antibody directed against the murine M-CSF receptor (c-fms). This reagent also inhibits in vitro colony formation by leukemic and normal rat splenocytes in response to M-CSF. At high antibody concentrations, the antibody augments, rather than inhibits, colony formation by rat cells in the presence of M-CSF, an effect that is not seen when murine cells are used as responders. The costimulatory and inhibitory activities of the monoclonal antibody preparations copurify in a number of purification methods, indicating that the costimulatory activity is intrinsic to the antireceptor antibody. Conversion of the antibody into monovalent Fab fragments by papain digestion destroys costimulatory activity. This finding raises a cautionary note for the in vivo use of intact monoclonal antibodies directed against growth factor receptors for the treatment of hematologic malignancies.
Shadduck
R K
RK
The Western Pennsylvania Cancer Institute, Pittsburgh 15224-2207, USA.
Fischer
B C
BC
DePasquale
D K
DK
Gilmore
G L
GL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D003433:Crosses, Genetic; D004306:Dose-Response Relationship, Immunologic; D004354:Drug Screening Assays, Antitumor; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006825:Hybridomas / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000503:physiopathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D013268:Stimulation, Chemical
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D015850:Interleukin-6; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor