Monoclonal antibody to ganglioside gq discriminates between haemopoietic cells and infiltrating neuroblastoma tumour cells in bone marrow

Abstract

An immunological approach has been sought for the identification of minimal metastatic spread of neuroblastoma to bone marrow. Here we describe the reactivity of the monoclonal antibody A2B5 to human neuroblastoma cell lines and fresh tumour tissue. This reagent, raised against chick retinal cells, reacts with all human neuroblastoma lines assayed although quantitative differences in antigenic expression exist between cultures. Analysis of tumour cells in heavily infiltrated bone marrow aspirates indicates that only 70% of the samples reacted with A2B5, suggesting that the heterogeneity seen in the expression of antigen on cell lines is paralleled in fresh tumour material. A2B5 showed no reactivity to either a panel of human leukaemic cell lines or normal human bone marrow, although reactivity to an occasional leukaemic marrow aspirate was detected. We suggest that A2B5 could form part of a panel of monoclonal reagents necessary for detecting metastatic spread of all neuroblastoma cells to bone marrow. Such a group of reagents may be useful therapeutically in a programmed of autologous bone marrow transplantation for the removal of tumour cells prior to reinfusion of haemopoietic cells to patients receiving high-dose chemotherapy.

Production and characterization of monoclonal antibodies against human neuroblastoma

“…MAb reactive with neuroblastoma cells were obtained from mice immunized with CHP-100 (Kemshead et al, 1981a) or IMR-6 (Jonak et al, 1982) neuroblastoma cells, human fetal brain (Kemshead et al, 1983) or chick retinal cells (Kemshead et al, 1981b). MAb exclusively reactive with all types and stages of neuroblastoma have not as yet been obtained.…”

Immunohistochemical performance testing of monoclonal antibodies to neuroblastoma cells on normal adrenals, spinal and sympathetic ganglia, and neural crest tumours

“…Kemshead and others (Kemshead et al 1981b, Moss et al 1985 have postulated that the variations in immunoreactivity seen with the various neuroblastoma antibodies reflect the different stages of maturation and differentiation in the neoplastic cells, comparable to what has been seen in haematological and lymphoid cell lines. The various neuroblastoma antibodies expressed different patterns of immunoreactivity in the normal neuroectodermally-derived structures.…”

“…A panel of 10 monoclonal antibodies to neuroblastoma cells was used (Table 1). Details concerning these reagents have been published previously (Eisenbarth, Walsh & Nirenberg 1979, Kennett & Gilbert 1979, 1981b, 1982, 1983a, b, Kemshead, Bicknell & Greaves 1981a. Performance testing was done on Table 1).…”

“…The heterogeneity seen in antigen expression between different samples may reflect variation in tumour cell differentiation in different cell lines and tumours. Such variation might reflect the normal development of the autonomic nervous system; normal differentiation of neuroectodermally-derived cells is likely to involve considerable modulation of cell surface antigens (Kemshead et al 1981b).…”

Human glioma associated and related antigens, identified by monoclonal antibodies

“…BF7 and GE2 of Schnegg defined glia-associated antigens [27], Me4-H4 and Me5-D5 of Carrel defined melanocyte-associated antigen [7], and A2B5 of Kemshead defined neuron-associated antigen [16]. There have been several reports of monoclonal antibodies against tumour specific antigens, although most of these antibodies have now been shown to react with some normal cells.…”