David V. Woo

Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: A phase II trial☆

Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months.

Indium-111-labeled anti-EGFr-425 scintigraphy in the detection of malignant gliomas.

Background. The monoclonal antibody anti‐epidermal growth factor receptor (EGFr)antibody‐425, against the epidermal growth factor receptor, has the potential to bind specifically to gliomas and not normal brain tissue.1–3 A prospective study was conducted (1986–1988) to evaluate the use of Indium‐111 (111In)‐labeled anti‐EGFr‐425 in the localization of gliomas before radioimmunotherapy with Iodine‐125 (125I)‐labeled anti‐EGFr‐425.

Enhancement of epidermal growth factor receptor expression on glioma cells by recombinant tumor necrosis factor α

SummaryRecombinant tumor necrosis factor α (rTNFα; optimal dose 1000 U/ml) significantly increased the density of epidermal growth factor receptor (EGF-R) in three of four glioma cell lines in culture as determined by binding analysis of anti-EGF-R monoclonal antibody (mAb) 425. Since enhancement of EGF-R expression by rTNF-α was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNFα may be protein-synthesis-dependent. The dose of rTNFα that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells.125I-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNFα, the growth-inhibitory effects of the mAb were significantly enhanced, probably a reflection of the increase in EGF-R density on the tumor cell surfaces. The rTNFα effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials,125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with125I-labeled mAb 425 and rTNFα.