Five novel cell surface antigens of CNS neoplasms

Jennings, Mark T.; Jennings, Vicki; Asadourian, Laura L.H.; Rosenblum, Marc K.; Albino, Anthony P.; Cairncross, J. Gregory; Old, Lloyd J.

doi:10.1016/0022-510x(89)90007-5

Cited by 12 publications

(5 citation statements)

References 18 publications

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“…Histologically identical tumors may arise in the pineal region, cerebrum, spinal cord, or brainstem and various classification systems assign names to these tumors based on their location (eg, pineoblastoma and cerebral neuroblastoma). Recognition that some PNETs contain cclls with the histological characteristics of neurons, glial cells (including ependyma), and, in rare instances, inuscle or melanocytes [2,29,[44][45][46][47] led to tumor nomenclature based on these characteristics [ 51. irrespective of the method of fixation [33,34,491. We found that the biological characteristics of PNETs are as prognostically significant as their clinical features (eg, tumor location and metastatic stage).…”

Section: Discussionmentioning

confidence: 99%

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Janss

Yachnis

Silber

et al. 1996

Annals of Neurology

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Primitive neuroectodermal tumors (PNETs) of the central nervous system, including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characteristic of glial differentiation (glial fibrillary acidic protein, GFAP), neuronal differentiation (neurofilament proteins, NFPs), and/or photoreceptor differentiation (retinal-S antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specimens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared with patient relapse-free survival. Multivariate analysis of PNET immunohistochemistry and clinical variables indicated GFAP expression conferred a 6.7-fold greater risk of relapse than tumors that did not express GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting clumps or sheets of GFAP-staining cells were associated with a 3.0-fold increased risk of relapse compared with tumors that did not express GFAP, irrespective of immunohistochemical evidence of other differentiation, while scattered GFAP staining was not associated with increased risk of relapse. These findings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used to predict clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Janss

Yachnis

Silber

et al. 1996

Annals of Neurology

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“…When syngeneic cells are used for immunization, the host is tolerant to 'self' antigens and the immune response is restricted to inappropriately-expressed fetal or normal antigens, or to 'neo' antigens, some of which may be expressed as a consequence of the malignant process [7,8,141. The weakness of the antibody response in the present study was not entirely surprising, given the syngeneic nature of the immunogens, the low inoculate level and relatively short immunization schedule, and the absence of adjuvant.…”

Section: Discussionmentioning

confidence: 99%

Production and evaluation of syngeneic antibodies showing specificity for the A15 A5 transplantable rat glioma

Clarke

Pilkington

1995

Neuropathology Appl Neurobio

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Antibodies have been raised which show specificity for the A15 A5 transplantable rat glioma model. Viable, irradiated, colcemid-treated and microwave-fixed A15 A5 cells were each used to hyperimmunize BDIX rats by subcutaneous inoculation, while viable cells were also injected intracerebrally into syngeneic animals. Specific anti-A15 A5 antibodies were detected in serum by a modified enzyme-linked immunoabsorbent assay (ELISA). Immunoperoxidase and immunofluorescence cytochemistry revealed the presence of antigen in paraffin-wax and frozen sections, respectively, of A15 A5 gliomas. The different methods of immunogen denaturation were found to affect the degree of immunological potency of the cells. This study has shown that A15 A5 cells are immunogenic in a syngeneic host. Intracerebrally transplanted, viable cells produced antibodies of higher titre than subcutaneously-injected, denatured cells. The anti-A15 A5 antisera may be used for detection of neoplastic rat astrocytes using immunocytochemistry. These antibodies will prove to be of value in discriminating between neoplastic and normal cells at the tumor/brain interface.

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“…The antigens defined by the mAbs CNT/2 and ASHE2 are expressed not only by medulloblastomas and gliomas, but also by normal brain tissue (Jones et al, 1984;Jennings et al, 1989). In addition, the mAbs UJ127-11, 5A7, FMG25, and M148 are reactive with medulloblastomas and neuroblastomas, but not with gliomas Gross et al, 1986;Gibson et al, 1987;Takahashi et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…The major reason for treatment failure is that recurrent tumours become insensitive to radiotherapy and chemotherapy (Pastan & Gottesman, 1987). In this situation, a potential new therapeutic approach is the utilisation of monoclonal antibodies, as is done for autologous bone marrow transplantation with purged bone marrow (Coombes et al, 1986).So far, ten monoclonal antibodies (mAbs) directed against medulloblastomas have been described Allan et al, 1983;Jones et al, 1984;Gross et al, 1986;Wikstrand et al, 1986;Gibson & Kemshead, 1987;Feickert et al, 1989;Jennings et al, 1989;Takahashi et al, 1990), but most of these antibodies also show reactivity with a broad range of other tumours and with normal tissues, making their in vivo use problematic.In the present study, we tried to develop mAbs with an increased specificity for medulloblastoma. Assuming that any mAb will have some degree of cross-reactivity with normal tissues, we selected those which at least did not react with peripheral blood cells or normal brain tissue, thus increasing the possibility of their future clinical application.…”

mentioning

confidence: 99%

“…So far, ten monoclonal antibodies (mAbs) directed against medulloblastomas have been described Allan et al, 1983;Jones et al, 1984;Gross et al, 1986;Wikstrand et al, 1986;Gibson & Kemshead, 1987;Feickert et al, 1989;Jennings et al, 1989;Takahashi et al, 1990), but most of these antibodies also show reactivity with a broad range of other tumours and with normal tissues, making their in vivo use problematic.…”

mentioning

confidence: 99%

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Characterisation of a new mouse monoclonal antibody (ONS-M21) reactive with both medulloblastomas and gliomas

Moriuchi

Shimizu²,

Miyao³

et al. 1993

Br J Cancer

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Summary We developed an IgGI mouse monoclonal antibody (ONS-M21) directed against a cell surface antigen of medulloblastomas and gliomas in immunisation of mice with the ONS-76 medulloblastoma cell line. The antibody specifically reacted with medulloblastomas, supratentorial primitive neuroectodermal tumours (SPNETs) and gliomas, but not with other neuroectodermally derived tumours (neuroblastoma and melanoma) or with other kinds of tumours (meningioma, neurinoma, leukaemia, and small cell lung cancer). No reactivity was identified with normal body tissues, including peripheral blood cells. Characterisation of the ONS-M21 antigen showed that it was a trypsin-sensitive glycoprotein with a molecular weight of 80 kDa on SDS-PAGE. The pattern of reactivity and the biochemical properties of this antigen were different from those of other markers of medulloblastoma. These results indicate that ONS-M21 detects a new tumour-associated cell surface antigen specifically expressed by medulloblastomas, SPNETs, and gliomas. This is the first report that medulloblastomas may share common cell surface antigens with gliomas, although most studies have concluded that medulloblastoma has a predominantly neuronal phenotype. The lack of reactivity with normal tissue implies that ONS-M21 has potential applications as both a diagnostic tool and a therapeutic agent.Medulloblastoma is the most common primitive neuroectodermal tumour (PNET) of the central nervous system in children (Rorke, 1983;Rorke et al., 1985;Dehner, 1986). The survival rate of patients with medulloblastoma has increased over the past four decades due to multiple factors, including improvement of surgical techniques and postoperative care, but mainly due to advances in whole-neuroaxis radiotherapy (Farwell et al., 1984;Hershatter et al., 1986). However, despite the recent advances in the treatment of many other childhood malignancies by combination chemotherapy, the long-term prognosis of medulloblastoma is still poor. The major reason for treatment failure is that recurrent tumours become insensitive to radiotherapy and chemotherapy (Pastan & Gottesman, 1987). In this situation, a potential new therapeutic approach is the utilisation of monoclonal antibodies, as is done for autologous bone marrow transplantation with purged bone marrow (Coombes et al., 1986).So far, ten monoclonal antibodies (mAbs) directed against medulloblastomas have been described Allan et al., 1983;Jones et al., 1984;Gross et al., 1986;Wikstrand et al., 1986;Gibson & Kemshead, 1987;Feickert et al., 1989;Jennings et al., 1989;Takahashi et al., 1990), but most of these antibodies also show reactivity with a broad range of other tumours and with normal tissues, making their in vivo use problematic.In the present study, we tried to develop mAbs with an increased specificity for medulloblastoma. Assuming that any mAb will have some degree of cross-reactivity with normal tissues, we selected those which at least did not react with peripheral blood cells or normal brain tissue, thus increasing the po...

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Five novel cell surface antigens of CNS neoplasms

Cited by 12 publications

References 18 publications

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Production and evaluation of syngeneic antibodies showing specificity for the A15 A5 transplantable rat glioma

Characterisation of a new mouse monoclonal antibody (ONS-M21) reactive with both medulloblastomas and gliomas

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