Growth Factor Receptor Expression Varies among High-Grade Gliomas and Normal Brain: Epidermal Growth Factor Receptor Has Excellent Properties for Interstitial Fusion Protein Therapy

• Published in: Molecular cancer therapeutics Vol. 2; no. 8; pp. 783 - 787
• Main Authors: Liu, Tie Fu, Tatter, Stephen B, Willingham, Mark C, Yang, Mitchell, Hu, Jennifer J, Frankel, Arthur E
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-08-2003
• Subjects: Astrocytoma - metabolism; Biomarkers, Tumor; Brain - metabolism; Brain Neoplasms - metabolism; Brain Neoplasms - therapy; Glioblastoma - metabolism; Glioma - metabolism; Glioma - therapy; Humans; Interleukin-13 Receptor alpha1 Subunit; Receptor, Epidermal Growth Factor - metabolism; Receptor, Epidermal Growth Factor - therapeutic use; Receptors, Interleukin - metabolism; Receptors, Interleukin-13; Receptors, Interleukin-4 - metabolism; Receptors, Transferrin - metabolism; Recombinant Fusion Proteins - therapeutic use; Tumor Cells, Cultured
• ISSN: 1535-7163; 1538-8514

Convection-enhanced delivery of fusion proteins is a novel therapeutic approach for patients with relapsed or refractory high-grade
gliomas. Multiple different fusion proteins have been produced that target different receptors on brain tumor cells. The sensitivity
of different gliomas to fusion proteins has been shown to depend in part on the expression of the target receptor. We undertook
a comparative study of the presence of the epidermal growth factor receptor (EGFR), interleukin-13 receptor (IL13R), interleukin-4
receptor (IL4R), and transferrin receptor (TfR) determined by immunofluorescence microscopy among fresh frozen tumor samples
from 38 patients with high-grade gliomas (glioblastoma multiforme or anaplastic astrocytoma). The frequency of high receptor
expression was 32 of 38 (84%) for EGFR, 30 of 38 (79%) for IL13R, 25 of 38 (66%) for TfR, and 17 of 38 (45%) for IL4R. Reactivity
of normal brain endothelium was observed for TfR, and reactivity of normal brain astrocytes was observed for IL4R. Because
of cross-reactivity of interleukin-13 with the IL4R-IL13Rα1 receptor, we infer reactivity of interleukin-13 with normal astrocytes.
In contrast, EGFR was not observed in normal brain. A number of patients (10 of 38 patients) showed unequal expression of
EGFR and IL13R. Thus, some patients may benefit more from interstitial therapy with an EGFR-directed fusion protein than from
therapy with an IL13R-directed fusion protein and vice versa . The safety profile may be improved with an agent directed to EGFR versus agents directed to TfR, IL4R, or IL13R. Design of clinical trials of fusion proteins in patients with brain tumors may be
enhanced by inclusion of relevant receptor density measurements.