Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors

Tumor-restricted surface antigens may be targets for diagnosis and immune-b ased therapies. Monoclonal antibody 8H9 is a murine IgG1 hybridoma derived from the fusion of mouse myeloma SP2/0 cells and splenic lymphocytes from B ALB/c mice immunized with human neuroblastoma. By immunohistochemistry, 8H9 was highly reactive with human brain tumors, childhood sarcomas, and neuro blastomas, and less so with adenocarcinomas. Among primary brain tumors, 15 of 17 glioblastomas, 3 of 3 mixed gliomas, 4 of 11 oligodendrogliomas, 6 o f 8 astrocytomas, 2 of 2 meningiomas, 3 of 3 schwannomas, 2 of 2 medullobla stomas, 1 of 1 neurofibroma, 1 of 2 neuronoglial tumors, 2 of 3 ependymomas , and 1 of 1 pineoblastoma tested positive. Among sarcomas, 21 of 21 Ewing' s/primitive neuroectodermal tumor, 28 of 29 rhabdomyosarcomas, 28 of 29 ost eosarcomas, 35 of 37 desmoplastic small round cell tumors, 2 of 3 synovial sarcomas, 4 of 4 leiomyosarcomas, 1 of 1 malignant fibrous histiocytoma, an d 2 of 2 undifferentiated sarcomas tested positive with 8H9. Eighty-seven o f 90 neuroblastomas, 12 of 16 melanomas, 3 of 4 hepatoblastomas, 7 of 8 Wil ms' tumors, 3 of 3 rhabdoid tumors, and 12 of 27 adenocarcinomas also teste d positive. In contrast, 8H9 was nonreactive with normal human tissues incl uding bone marrow, colon, stomach, heart, lung, muscle, thyroid, testes, pa ncreas, and human brain (frontal lobe, cerebellum, pens, and spinal cord). Reactivity with normal cynomolgus monkey tissue was restricted similarly. I ndirect immunofluorescence localized the antigen recognized by 8H9 to the c ell membrane. The antigen is proteinase sensitive and is not easily modulat ed off the cell surface. 8H9 immunoprecipitated a M, 58,000 band after N-gl ycanase treatment, most likely a protein with a heterogeneous degree of gly cosylation. This novel antibody-antigen system may have potential for tumor targeting.