HER/erbB Receptors as Therapeutic Targets of Immunotoxins in Human Rhabdomyosarcoma Cells
作者:
Cinzia Ricci,
Letizia Polito,
Patrizia Nanni,
Lorena Landuzzi,
Annalisa Astolfi,
Giordano Nicoletti,
Ilaria Rossi,
Carla De Giovanni,
Andrea Bolognesi,
Pier-Luigi Lollini,
期刊:
Journal of Immunotherapy
(OVID Available online 2002)
卷期:
Volume 25,
issue 4
页码: 314-323
ISSN:1524-9557
年代: 2002
出版商: OVID
关键词: HER/ErbB receptors;Rhabdomyosarcoma;Immunotoxins;Protein synthesis;Apoptosis
数据来源: OVID
摘要:
Human rhabdomyosarcoma cells express HER/erbB growth factors receptors. Receptors belonging to this family are overexpressed and play a role in many types of epithelial and neural cancer and have been selected as targets for cancer therapy. In this paper EGF-R, HER-2 and HER-3 receptors were tested as therapeutic targets of immunotoxins in human rhabdomyosarcoma. Rhabdomyosarcoma cells were treated with indirect immunotoxins consisting in primary specific murine monoclonal antibodies recognizing EGF-R, HER-2 and HER-3 followed by secondary F(ab´)2antimouse immunoglobulin linked to saporin-S6, a type 1 ribosome-inactivating protein (RIP) from the seeds ofSaponaria officinalis. The indirect immunotoxin targeting EGF-R caused a significant inhibition in cell growth and protein synthesis and a strong increase in apoptosis in rhabdomyosarcoma cells, whereas indirect immunotoxins against HER-2 and HER-3 were ineffective. The toxic activity of anti-EGF-R immunotoxin was also observed on rhabdomyosarcoma cells expressing low level of EGF-R. EGF-R could be a novel therapeutic target of immunotoxins in human rhabdomyosarcoma.
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