MONOCLONAL-ANTIBODY TO HUMAN TRK-A - DIAGNOSTIC AND THERAPEUTIC POTENTIAL IN NEUROBLASTOMA

5C3 is a murine IgG(1) antibody specific for the nerve growth factor ( NGF) docking site of the human p140 trk-A receptor, with no cross-reac tivity with human trk-B. In vitro, 5C3 and its Fab mimic the effects o f NGF, a neurotrophin mediating growth and differentiation of neural c rest-derived cells. When labelled with radioisotope, 5C3 images human trk-A positive tumours in vivo. More importantly, 5C3 induces regressi on of human trk-A positive tumours in rodents. We therefore investigat ed the value of 5C3 in detecting trk-A expression in human neuroblasto ma by immunohistochemistry. 5C3 reactivity was detected in 73 of 113 n euroblastoma specimens and correlated strongly with localised/4s disea se (55/60) with either a homogeneous or mixed pattern. Among stage 4 n euroblastoma, only 18/53 had homogeneous or mixed trk-A expression. 5C 3 did not-react with 46/48 other human malignancies, but was positive in 1 melanoma and 1 Wilms' tumour specimen. The prognostic, imaging an d NGF-mimetic properties of antibody 5C3 and its derivatives may offer alternatives for the diagnosis and treatment of neuroblastoma. (C) 19 97 Elsevier Science Ltd.