Activity of Anti-epidermal Growth Factor Receptor Monoclonal Antibody C225 against Glioblastoma Multiforme

Eller, Jorge L.; Longo, Sharon L.; Hicklin, Daniel J.; Canute, Gregory W.

doi:10.1097/00006123-200210000-00028

Cited by 63 publications

(51 citation statements)

References 38 publications

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“…We speculated that targeting residual malignant gliomas should be quick, especially considering the fact of their high radioresistence. (27,28) The analysis of intralesional uptake of radioiodinated Mab 425 labeled with 131 I, carried out in one patient with residual disease before this study, indicated that 5-7 Gy may be supplied by a course of 40-50 mCi of anti-EGFR 1 125 I-MAb 425 RIT. Based on earlier results in vitro, (27) one could expect a beneficial effect of the combined treatment.…”

Section: Figmentioning

confidence: 82%

“…MAb 425, a murine IgG2a derived from hybridoma established after immunization of BALB/c mice with the A431 human epidermoid carcinoma cell line, (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) was obtained as a 10 mg/mL solution in saline. Five milligrams of antibody was used for each radioiodination with the Iodogen method, performed in a closed system glove box under lowered pressure.…”

Section: Monoclonal Antibody and Its Radioiodinationmentioning

confidence: 99%

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Use of Monoclonal Anti-EGFR Antibody in the Radioimmunotherapy of Malignant Gliomas in the Context of EGFR Expression in Grade III and IV Tumors

Wygoda

Kula²,

Bierzyńska-Macyszyn³

et al. 2006

Hybridoma

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We investigated the putative benefits of simultaneous teleradiotherapy and anti-epidermal growth factor receptor (EGFR) 125I monoclonal antibody (MAb) 425 radioimmunotherapy, when applied after neurosurgery in high-grade gliomas, over teleradiotherapy alone. In comparison to previous studies which have reported good results with this type of radioimmunotherapy, we advanced the adjuvant radioimmunotherapy step, that is, gave it during, not after, teleradiotherapy. The randomized prospective study examined two groups: simultaneous postoperative teleradiotherapy and radioimmunotherapy (TRT + RIT; eight patients) versus teleradiotherapy alone (TRT; 10 patients). Patients who after primary operation of grade III (6 cases) or IV glioma (12 cases), showed no or less than 2 mL of remnant tumor on post-operative magnetic resonance (MR) study and were not treated postoperatively by chemotherapy were enrolled and randomized. Anti-EGFR 125IMAb 425 RIT was started during week 4 of radiotherapy, not later than 8 weeks after neurosurgery, and was repeated three times at 1-week intervals. Total activity given was 5026 + 739 MBq/patient. The tolerance of TRT was good. No immediate side effects of concomitant anti-EGRF 125I RIT were observed. Observation showed a median total survival (as evaluated from the primary neurosurgical treatment) of 14 months (range 3.5-28 months). There was no improvement in disease-free or total survival in the group of patients treated by TRT + RIT after neurosurgery. In addition, an immunohistochemical analysis of EGFR expression in gliomas was performed in a group of 100 cases and was distinctly positive in 50% grade IV gliomas and 68% grade III gliomas. We conclude that simultaneous radiotherapy and radioimmunotherapy with anti-EGFR 125I-MAb 425 is not beneficial over radiotherapy alone in adjuvant treatment of high-grade gliomas after neurosurgery. We also recommend individual confirmation of EGFR expression in further anti-EGFR radioimmunotherapy trials.

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Section: Figmentioning

confidence: 82%

Section: Monoclonal Antibody and Its Radioiodinationmentioning

confidence: 99%

Use of Monoclonal Anti-EGFR Antibody in the Radioimmunotherapy of Malignant Gliomas in the Context of EGFR Expression in Grade III and IV Tumors

Wygoda

Kula²,

Bierzyńska-Macyszyn³

et al. 2006

Hybridoma

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“…There are conflicting data, however, regarding whether EGFR amplification imparts cetuximab sensitivity. Supporting this association, one study demonstrated cetuximab-induced cytotoxicity in EGFR-amplified GBM cell lines but not in the cell lines without amplification [33]. Also in support of this link, another in vitro study demonstrated additive cytotoxic effects against EGFR-amplified GBM with the combination of cetuximab and radiation.…”

mentioning

confidence: 89%

Targeting the Epidermal Growth Factor Receptor in High-Grade Astrocytomas

Voelzke

Petty

Lesser

2008

Curr. Treat. Options in Oncol.

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High-grade astrocytomas, including glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), are the most common and aggressive primary malignant brain tumors in adults. Despite improvements in survival with the addition of temozolomide to radiation in the adjuvant setting, the prognosis of patients affected by these tumors remains relatively poor. One approach to improve outcomes in these patients is to target the epidermal growth factor receptor (EGFR). EGFR-targeted therapy is a rational approach since EGFR overexpression and mutant EGFRvIII expression occur in approximately 50% of patients with GBM. Unfortunately, monotherapy with anti-EGFR agents in malignant gliomas has not provided the dramatic results sometimes seen with other targeted therapies, such as imatinib in chronic myelogenous leukemia. Anti-EGFR agents currently being studied in malignant gliomas include the tyrosine kinase inhibitors (TKI), monoclonal antibodies (MAb), and anti-EGFR vaccines. Of all these agents, the tyrosine kinase inhibitors-which include erlotinib and gefitinib-have been the most extensively tested in clinical trials. Retrospective analyses have highlighted co-expression of EGFRvIII and wild-type PTEN (phosphatase and tensin homologue deleted in chromosome 10) as a significant predictor of EGFR TKI response in patients with GBM. As the EGFR signaling pathway is exceptionally complex, newer approaches targeting multiple points in the pathway are being developed to improve treatment efficacy.

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“…46 Two other antibodies, MAb 528 47 and the human-mouse chimeric MAb cetuximab (IMC-C225, Erbitux, ImClone Systems, Inc., New York, NY) 48;49 have been shown to inhibit glioma proliferation in vitro and in vivo and cetuximab was also able to promote apoptosis and decrease EGFR-mediated VEGF production. 49 These MAbs have not been clinically trialled in gliomas, however, because of disappointing results against lung cancer.…”

Section: Monoclonal Antibodies: Glioma Therapymentioning

confidence: 99%

Targeted therapy for malignant gliomas

Morokoff¹,

Novak²

2004

Journal of Clinical Neuroscience

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Activity of Anti-epidermal Growth Factor Receptor Monoclonal Antibody C225 against Glioblastoma Multiforme

Abstract: Blocking EGFR in GBM cells that overexpress this receptor significantly changes tumor cell biology by promoting apoptosis while decreasing proliferation and vascular endothelial growth factor expression. This approach holds great promise for the treatment of patients with GBMs.

Cited by 63 publications

References 38 publications

Use of Monoclonal Anti-EGFR Antibody in the Radioimmunotherapy of Malignant Gliomas in the Context of EGFR Expression in Grade III and IV Tumors

Use of Monoclonal Anti-EGFR Antibody in the Radioimmunotherapy of Malignant Gliomas in the Context of EGFR Expression in Grade III and IV Tumors

Targeting the Epidermal Growth Factor Receptor in High-Grade Astrocytomas

Targeted therapy for malignant gliomas

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