Growth factor receptor expression varies among high-grade gliomas and normal brain

Epidermal growth factor receptor has excellent properties for interstitial fusion protein therapy

Tie Fu Liu, Stephen B. Tatter, Mark C. Willingham, Mitchell Yang, Jennifer J. Hu, Arthur E. Frankel

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)783-787
Number of pages5
JournalMolecular Cancer Therapeutics
Volume2
Issue number8
StatePublished - Aug 2003

Fingerprint

Interleukin-13 Receptors
Interleukin-4 Receptors
Growth Factor Receptors
Epidermal Growth Factor Receptor
Glioma
Transferrin Receptors
Brain
Proteins
Interleukin-13
Brain Neoplasms
Astrocytes
Type II Interleukin-4 Receptors
Therapeutics
Convection
Astrocytoma
Glioblastoma
Fluorescence Microscopy
Endothelium
Clinical Trials
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Drug Discovery
  • Pharmacology

Cite this

Growth factor receptor expression varies among high-grade gliomas and normal brain : Epidermal growth factor receptor has excellent properties for interstitial fusion protein therapy. / Liu, Tie Fu; Tatter, Stephen B.; Willingham, Mark C.; Yang, Mitchell; Hu, Jennifer J.; Frankel, Arthur E.

In: Molecular Cancer Therapeutics, Vol. 2, No. 8, 08.2003, p. 783-787.

Research output: Contribution to journalArticle

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