Inhibition of growth of mouse leukemic cell lines in vitro and in vivo by a monoclonal antibody that recognizes an interleukin 3 receptor-associated protein.
Myeloid cell lines that have achieved leukemic transformation may also have acquired the ability to produce hematopoietic growth factors. In certain instances, neutralizing antibodies directed against the growth factor have inhibited growth, supporting an autocrine mechanism in their transformation. The effect of anti-receptor antibodies on their growth and transformed phenotype has not been reported. We have developed a monoclonal antibody, 4G8, directed against a protein that is associated with the IL-3 receptor complex; 4G8 inhibits IL-3 binding and signal transduction in nonleukemic IL-3-dependent cell lines. In this study, we examined the effect of 4G8 on the growth in vitro and in vivo of leukemic cell lines, including WEHI-3B, which spontaneously produces IL-3, and NFS-60, an IL-3-dependent cell line. Our results demonstrate that the 4G8 antigen can be detected in both WEHI-3B and NFS-60 cells by flow cytometry and Western blotting; 4G8 inhibits the autonomous growth of WEHI-3B and the IL-3-dependent growth of both WEHI-3B and NFS-60. In addition, s.c. administration of 4G8 prolonged the survival of syngeneic mice given s.c. injections of WEHI-3B. These results support the conclusion that an autocrine mechanism involving IL-3 and its receptor plays a critical role in the growth and transformed phenotype of WEHI-3B and raises the possibility that anti-IL-3 receptor antibodies may be useful in the treatment of some leukemias.
Tweardy
D J
DJ
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
Morel
P A
PA
Herberman
R B
RB
Sakurai
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D005434:Flow Cytometry; D007167:Immunotherapy; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D016185:Receptors, Interleukin-3 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D016185:Receptors, Interleukin-3