Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma |
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Authors: | P. Wersäll I. Ohlsson P. Biberfeld V. P. Collins S. von Krusenstjerna S. Larsson H. Mellstedt J. Boethius |
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Affiliation: | (1) Department of Oncology, (Radiumhemmet), Karolinska Hospital, S-17176 Stockholm, Sweden Fax: +47 8 31 15 85, SE;(2) Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden, SE;(3) Department of Pathology, Karolinska Hospital, Stockholm, Sweden, SE;(4) Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden, SE;(5) Department of Experimental Oncology, Uppsala University, Uppsala, Sweden, SE |
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Abstract: | Malignant glioblastoma may over-express the epidermal-growth-factor receptor (EGF-R). Normal brain cells show a low or no expression of EGF-R. A mouse monoclonal antibody (IgG2A) (mAb 425) (EMD55900) (Merck KGaA, Bernstadt, Germany) directed against EGF-R was produced for therapeutic use. Eight patients with primary or recurrent, EGF-R-positive glioblastomas entered the study, which was designed to evaluate the clinical effect of the mAb. In order to achieve a high tumor cell saturation, the mAb was injected intratumorally twice weekly through an implantable catheter. The total administered dose varied between 4 mg and 120 mg. In 3 patients with solid tumors, a massive tumor necrosis was noted, with infiltration of macrophages, granulocytes and T cells. A further 3 patients developed clinical and radiological signs of an intense, local, inflammatory reaction. There may be a relation between the mAb dosage and the antitumor effect, insofar as higher doses seemed to cause a more pronounced, inflammatory reaction. Of the 8 patients, 6 developed human, anti-(mouse Ig) antibodies. This anti-EGF-R mAb may induce an intense, inflammatory reaction and a considerable necrosis in glioblastoma. However, the planned schedule could not be completed, even after the dose level was re-adjusted, owing to inflammatory reactions, which were severe without prior tumor debulking. Received: 12 November 1996 / Accepted: 3 March 1997 |
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Keywords: | Epidermal growth factor Murine monoclonal antibody Glioma Immunotherapy |
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