Human monoclonal antibody with dual GM2/GD2 specificity derived from an immunized melanoma patient.
GM2 ganglioside is a common cell surface constituent of human melanoma and other tumors of neuroectodermal origin, and vaccination with GM2 ganglioside results in high levels of anti-GM2 antibodies in patients with melanoma. Lymphocytes from a GM2-vaccinated patient (VS) were transformed by Epstein-Barr virus and tested for production of antibodies with reactivity for GM2-positive tumor cells. A high percentage of antibody-producing B cells was detected, but antibody reactivity was generally lost during culture expansion. Two cultures, however, remained stable for antibody productivity and one was used to develop a stable hybrid line with mouse myeloma. The monoclonal antibody (designated 3-207) derived from patient VS has dual specificity for GM2 and GD2, despite the fact that only GM2 antibody could be detected in the patient's serum. Monoclonal antibody 3-207 shows high-titered reactivity with a range of melanoma, astrocytoma, neuroblastoma, and leukemia cell lines, cells with prominent cell surface expression of GM2 and GD2. The cell surface reactivity of monoclonal antibody 3-207 was not abolished by treatment of target cells with neuraminidase, as the enzyme converted GD2 to GM2, which was still detected by monoclonal antibody 3-207.
Yamaguchi
H
H
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Furukawa
K
K
Fortunato
S R
SR
Livingston
P O
PO
Lloyd
K O
KO
Oettgen
H F
HF
Old
L J
LJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D001500:BCG Vaccine; D002459:Cell Fusion; D002460:Cell Line; D002472:Cell Transformation, Viral; D002855:Chromatography, Thin Layer; D005678:G(M2) Ganglioside / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology* / Q000302:isolation & purification; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase; D014407:Tumor Cells, Cultured / Q000276:immunology*; D014612:Vaccines
D000911:Antibodies, Monoclonal; D001500:BCG Vaccine; D005732:Gangliosides; D014612:Vaccines; D005678:G(M2) Ganglioside; C019403:ganglioside, GD2; D009439:Neuraminidase