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

S. Modak, K. Kramer, Sakir Gultekin, H. F. Guo, N. K V Cheung

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Tumor-restricted surface antigens may be targets for diagnosis and immune-based therapies. Monoclonal antibody 8H9 is a murine IgG1 hybridoma derived from the fusion of mouse myeloma SP2/0 cells and splenic lymphocytes from BALB/c mice immunized with human neuroblastoma. By immunohistochemistry, 8H9 was highly reactive with human brain tumors, childhood sarcomas, and neuroblastomas, and less so with adenocarcinomas. Among primary brain tumors, 15 of 17 glioblastomas, 3 of 4 mixed gliomas, 4 of 11 oligodendrogliomas, 6 of 8 astrocytomas, 2 of 2 meningiomas, 3 of 3 schwannomas, 2 of 2 medulloblastomas, 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 osteosarcomas, 35 of 37 desmoplastic small round cell tumors, 2 of 3 synovial sarcomas, 4 of 4 leiomyosarcomas, 1 of 1 malignant fibrous histiocytoma, and 2 of 2 undifferentiated sarcomas tested positive with 8H9. Eighty-seven of 90 neuroblastomas, 12 of 16 melanomas, 3 of 4 hepatoblastomas, 7 of 8 Wilms' tumors, 3 of 3 rhabdoid tumors, and 12 of 27 adenocarcinomas also tested positive. In contrast, 8H9 was nonreactive with normal human tissues including bone marrow, colon, stomach, heart, lung, muscle, thyroid, testes, pancreas, and human brain (frontal lobe, cerebellum, pons, and spinal cord). Reactivity with normal cynomolgus monkey tissue was restricted similarly. Indirect immunofluorescence localized the antigen recognized by 8H9 to the cell membrane. The antigen is proteinase sensitive and is not easily modulated off the cell surface. 8H9 immunoprecipitated a Mr 58,000 band after N-glycanase treatment, most likely a protein with a heterogeneous degree of glycosylation. This novel antibody-antigen system may have potential for tumor targeting.

Original languageEnglish (US)
Pages (from-to)4048-4054
Number of pages7
JournalCancer Research
Volume61
Issue number10
StatePublished - May 15 2001
Externally publishedYes

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Surface Antigens
Neuroblastoma
Sarcoma
Antigens
Brain Neoplasms
Neoplasms
Adenocarcinoma
Desmoplastic Small Round Cell Tumor
Rhabdoid Tumor
Pinealoma
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Hepatoblastoma
Synovial Sarcoma
Oligodendroglioma
Primitive Neuroectodermal Tumors
Ependymoma
Malignant Fibrous Histiocytoma
Neurofibroma
Medulloblastoma
Macaca fascicularis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Modak, S., Kramer, K., Gultekin, S., Guo, H. F., & Cheung, N. K. V. (2001). Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Research, 61(10), 4048-4054.

Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. / Modak, S.; Kramer, K.; Gultekin, Sakir; Guo, H. F.; Cheung, N. K V.

In: Cancer Research, Vol. 61, No. 10, 15.05.2001, p. 4048-4054.

Research output: Contribution to journalArticle

Modak, S, Kramer, K, Gultekin, S, Guo, HF & Cheung, NKV 2001, 'Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors', Cancer Research, vol. 61, no. 10, pp. 4048-4054.
Modak S, Kramer K, Gultekin S, Guo HF, Cheung NKV. Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Research. 2001 May 15;61(10):4048-4054.
Modak, S. ; Kramer, K. ; Gultekin, Sakir ; Guo, H. F. ; Cheung, N. K V. / Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. In: Cancer Research. 2001 ; Vol. 61, No. 10. pp. 4048-4054.
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