The cytotoxicity of a conjugate composed of human epidermal growth factor and eosinophil cationic protein.
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.


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.


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.


CONCLUSIONS
Conjugates composed solely of human proteins might be useful with less immunogenicity and less toxicity than the conventional immunotoxins for targeted therapy.
Jinno
Hiromitsu
H
Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan.
Ueda
Masakazu
M
Ozawa
Soji
S
Ikeda
Tadashi
T
Kitajima
Masaki
M
Maeda
Takashi
T
Seno
Masaharu
M
D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry; D047091:Eosinophil Granule Proteins; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012260:Ribonucleases; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D004220:Disulfides; D047091:Eosinophil Granule Proteins; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D012260:Ribonucleases