Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma.
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.
Wersäll
P
P
Department of Oncology, (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
Ohlsson
I
I
Biberfeld
P
P
Collins
V P
VP
von Krusenstjerna
S
S
Larsson
S
S
Mellstedt
H
H
Boethius
J
J
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D051379:Mice; D008875:Middle Aged; D012008:Recurrence
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors