Journal
JOURNAL OF IMMUNOTHERAPY
Volume 25, Issue 4, Pages 314-323Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00002371-200207000-00003
Keywords
HER/ErbB receptors; rhabdomyosarcoma; immunotoxins; protein synthesis; apoptosis
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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')(2) antimouse immunoglobulin linked to saporin-S6, a type I ribosome-inactivating protein (RIP) from the seeds of Saponaria 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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