Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen.

Epenetos, A A; Courtenay-Luck, Nigel; Pickering, Darren; Hooker, G; Durbin, Helga; Lavender, J. P.; McKenzie, Craig R. M.

doi:10.1136/bmj.290.6480.1463

Cited by 124 publications

(29 citation statements)

References 11 publications

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“…In contrast to anti-idiotypic antibodies, though, the anti-fusion junction peptide antibody may react, not with just one patient's tumor, but rather with the tumors of all patients with this particular EGFR deletion mutation. Immunoimaging and immunotherapy have been performed with antibodies reactive against brain tumors, including antibodies reactive against the intact EGFR in gliomas (27,28). However, the molecules thus far targeted in brain tumors, such as the intact EGFR, are also expressed by normal tissues, thereby limiting the amount of antibody delivered to tumor and potentially leading to normal tissue toxicity.…”

Section: Discussionmentioning

confidence: 99%

Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma.

Humphrey

Wong

Vogelstein

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

342

188

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We have investigated human gliomas that amplify and rearrange the epidermal growth factor receptor gene, with generation of an in-frame deletion mutation of 802 nucleotides in the external domain. This in-frame deletion mutation generates a local amino acid sequence at the fusion junction of what normally were distant polypeptide sequences in the intact epidermal growth factor receptor. This 14-amino acid peptide was chemically synthesized, coupled to keyhole limpet hemocyanin, and used as an immunogen in rabbits. The elicited antibody reacted specifically with the fusion peptide in ELISA. The anti-fusion junction peptide antibody was purified by passage of the antiserum over a peptide affinity column with acidic elution. The purified antibody selectively bound the glioma deletion mutant as compared to the intact epidermal growth factor receptor as assessed by immunocytochemistry, immunofluorescence, immunoprecipitation with gel electrophoresis, and binding experiments using radioiodinated antibody. These data indicate that it is feasible to generate sitespecific anti-peptide antibodies that are highly selective for mutant proteins in human tumors. The anti-peptide antibody described here, and other mutation site-specific antibodies, should be ideal candidates for tumor immunoimaging and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma.

Humphrey

Wong

Vogelstein

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

342

188

View full text Add to dashboard Cite

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“…Study of this is currently hampered by the lack of immunological reagents which reliably detect EGF receptor expression in paraffin embedded archival material. The high levels of receptor expression do however provide a target for immunoscintigraphy (Takahashi et al, 1987) and immunotherapy (Epenetos et al, 1985;Kalofonos et al, 1989) and novel forms of receptor inhibitors (Gullick, 1990 (Slamon et al, 1989;Gullick et al, 1990), stomach (Falck & Gullick, 1989) and ovarian cancers (Slamon et al, 1989) and with a lower frequency in other tumour types (Hall et al, 1990;Yokota et al, 1986;Lemoine et al, 1990b). The c-erbB-2 protein, detected by Western blotting, was expressed at low, variable levels in the cell lines, but not in the primary tumour biopsies.…”

Section: Egf Receptormentioning

confidence: 99%

Expression of growth factor receptors in human brain tumours

Tuzi

Venter²,

Kumar³

et al. 1991

Br J Cancer

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Summary The expression of the EGF receptor, c-erbB-2 and PDGF receptor proteins has been studied in a series of human brain tumour biopsies and cell lines. Western blotting was used to determine the amount of protein present and their intrinsic and ligand promoted enzyme activities were studied by immunoprecipitation followed by autophosphorylation. EGF receptors were found to be expressed at very high levels in 40% of primary tumour biopsies, but at uniformly low levels in tumour derived cell lines. The c-erbB-2 protein was not detected in tumour biopsies, but was present at variable, but low levels in extracts of tumour cell lines. PDGF receptors were also found at moderate to low levels in both primary tumours and cell lines. The EGF receptor gene was amplified in four out of 14 primary tumours and this generally correlated with high levels of protein expression. The c-erbB-2 gene was not amplified. Employing the polymerase chain reaction and sequence specific oligonucleotides as probes there was no evidence of mutations in the c-erbB-2 gene transmembrane region. These results suggest that alterations of expression of the EGF receptor may play a role in human brain tumours. There was however no evidence for aberrant expression of the c-erbB-2 protein.Additional experiments are required to assess the influence of PDGF receptor expression in brain tumour cells.

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“…2,18,27 Several tumor clinical trials have shown that localization of monoclonal antibodies to the brain is poor without BBBD (0.0006%-0.0043% of the injected dose/ gram of tumor). 4,8,13,17,25,26 There is also evidence of a 20-fold increase in permeability to immunoreactive immunoglobulin M monoclonal antibody with BBBD in rats. 17 Based on these findings, BBBD may also significantly increase delivery of bevacizumab to the brain.…”

Section: Blood-brain Barrier Disruptionmentioning

confidence: 99%

Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain

Dashti

Spalding

Kadner

et al. 2015

PED

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Radiation necrosis (RN) is a serious complication that can occur in up to 10% of brain radiotherapy cases, with the incidence dependent on both dose and brain location. Available medical treatment for RN includes steroids, vitamin E, pentoxifylline, and hyperbaric oxygen. In a significant number of patients, however, RN is medically refractory and the patients experience progressive neurological decline, disabling headaches, and decreased quality of life. Vascular endothelial growth factor (VEGF) is a known mediator of cerebral edema in RN. Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF. Bevacizumab, however, is associated with significant systemic complications including sinus thrombosis, pulmonary embolus, gastrointestinal tract perforation, wound dehiscence, and severe hypertension. Using lower drug doses may decrease systemic exposure and reduce complication rates. By using an intraarterial route for drug administration following blood-brain barrier disruption (BBBD), the authors aim to lower the bevacizumab dose while increasing target delivery. In the present report, the authors present the cases of 2 pediatric patients with cerebral arteriovenous malformations, who presented with medically intractable RN following stereotactic radiosurgery. They received a single intraarterial infusion of 2.5 mg/kg bevacizumab after hyperosmotic BBBD. At mean follow-up duration of 8.5 months, the patients had significant and durable clinical and radiographic response. Both patients experienced resolution of their previously intractable headaches and reversal of cushingoid features as they were successfully weaned off steroids. One of the patients regained significant motor strength. There was an associated greater than 70% reduction in cerebral edema. Intraarterial administration of a single low dose of bevacizumab after BBBD was safe and resulted in durable clinical and radiographic improvements at concentrations well below those required for the typical systemic intravenous route. Advantages over the intravenous route may include higher concentration of drug delivery to the affected brain, decreased systemic toxicity, and a significantly lower cost.

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Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen.

Abstract: In a patient with recurrent grade IV glioma of the brain resistant to conventional treatment an antibody guided isotopic scan showed uptake by the tumour of a monoclonal antibody (9A) that was developed against epidermal growth factor receptor but cross reacted with

Cited by 124 publications

References 11 publications

Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma.

Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma.

Expression of growth factor receptors in human brain tumours

Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain

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