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The cytotoxicity of a conjugate composed of human epidermal growth factor and eosinophil cationic protein.
- Source :
-
Anticancer research [Anticancer Res] 2002 Nov-Dec; Vol. 22 (6C), pp. 4141-5. - Publication Year :
- 2002
-
Abstract
- Background: Conventional targeted therapy with foreign proteins is highly immunogenic. In this study, we developed targeted therapy composed of human endogenous proteins and evaluated its efficacy in vitro.<br />Materials and Methods: Human epidermal growth factor (EGF) was chemically linked to human eosinophil cationic protein (ECP). The cytotoxicity of the EGF-ECP conjugate was evaluated by MTT assay.<br />Results: The conjugate showed dose-dependent cytotoxicity on EGF receptor (EGFR)-overexpressing BT-20 cells with an IC50 of 1.5 x 10(-7) M, whereas the IC50 of ECP alone was almost 10(-4) M. The conjugate had no detectable cytotoxicity against EGF receptor-deficient H69 cells. Excess EGF protected BT-20 cells from the cytotoxicity of the conjugate. Comparing the cytotoxicity and the level of EGFR expression, the cytotoxicity of the conjugate was positively correlated with the level of EGFR expression of each cell line.<br />Conclusion: Conjugates composed solely of human proteins might be useful with less immunogenicity and less toxicity than the conventional immunotoxins for targeted therapy.
- Subjects :
- Blood Proteins chemistry
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Carcinoma, Small Cell drug therapy
Carcinoma, Small Cell metabolism
Disulfides chemistry
Eosinophil Granule Proteins
Epidermal Growth Factor chemistry
Epidermal Growth Factor metabolism
ErbB Receptors biosynthesis
ErbB Receptors metabolism
Humans
Inhibitory Concentration 50
Lung Neoplasms drug therapy
Lung Neoplasms metabolism
Recombinant Proteins chemistry
Recombinant Proteins pharmacology
Tumor Cells, Cultured
Blood Proteins pharmacology
Epidermal Growth Factor pharmacology
Ribonucleases
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 22
- Issue :
- 6C
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 12553045