Generation of a monoclonal antibody agonist to toll-like receptor 4.
Toll-Like Receptor 4 (TLR4) has recently been identified as the lipopolysaccharide (LPS) receptor. Upon stimulation of TLR4 with LPS, a Th1 type cytokine response is observed. This immune modulation is thought to have a potential benefit in anti-tumor therapy. We have generated a TLR4 antibody agonist (5D24.D4) that mimics the action of the natural ligand. 5D24.D4 and LPS stimulation of TLR4 leads to a similar response, including IL-8 secretion, activation of NF-kB-mediated transcription, and the induced expression of an overlapping set of target genes. 5D24.D4 may be beneficial as an adjuvant anti-tumor therapy.
Cohen
S B
SB
Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. scohen@gnf.org
Gaskins
C
C
Nasoff
M S
MS
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005786:Gene Expression Regulation; D006801:Humans; D006825:Hybridomas; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008070:Lipopolysaccharides / Q000378:metabolism*; D008156:Luciferases; D008562:Membrane Glycoproteins / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011956:Receptors, Cell Surface / Q000819:agonists / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014158:Transcription, Genetic / Q000502:physiology
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D008156:Luciferases