Monoclonal antibody to human Trk-A: diagnostic and therapeutic potential in neuroblastoma.
5C3 is a murine IgG1 antibody specific for the nerve growth factor (NGF) docking site of the human p140 trk-A receptor, with no cross-reactivity with human trk-B. In vitro, 5C3 and its Fab mimic the effects of NGF, a neurotrophin mediating growth and differentiation of neural crest-derived cells. When labelled with radioisotope, 5C3 images human trk-A positive tumours in vivo. More importantly, 5C3 induces regression of human trk-A positive tumours in rodents. We therefore investigated the value of 5C3 in detecting trk-A expression in human neuroblastoma by immunohistochemistry. 5C3 reactivity was detected in 73 of 113 neuroblastoma specimens and correlated strongly with localised/4s disease (55/60) with either a homogeneous or mixed pattern. Among stage 4 neuroblastoma, only 18/53 had homogeneous or mixed trk-A expression. 5C3 did not react with 46/48 other human malignancies, but was positive in 1 melanoma and 1 Wilms' tumour specimen. The prognostic, imaging and NGF-mimetic properties of antibody 5C3 and its derivatives may offer alternatives for the diagnosis and treatment of neuroblastoma.
Kramer
K
K
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Gerald
W
W
LeSauteur
L
L
Saragovi
H U
HU
Cheung
N K
NK
D000911:Antibodies, Monoclonal; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D009447:Neuroblastoma / Q000175:diagnosis* / Q000378:metabolism; D020917:Receptor, trkA / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D020917:Receptor, trkA