Great news! The concept was reported less than two years ago. Looks like they are making good progress. [See also Lani's thread:
http://her2support.org/vbulletin/sho...ight=Affitoxin ]
J Immunother. 2009 Oct;32(8):817-25.
Affitoxin--a novel recombinant, HER2-specific, anticancer agent for targeted therapy of HER2-positive tumors.
Zielinski R,
Lyakhov I,
Jacobs A,
Chertov O,
Kramer-Marek G,
Francella N,
Stephen A,
Fisher R,
Blumenthal R,
Capala J.
Source
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract
Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in 25% to 30% of breast cancers and has been associated with an unfavorable prognosis. Here we report the construction, purification, and characterization of
Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2-specific Affibody molecule as a targeting moiety and PE38KDEL, which is a truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is highly soluble and does not require additional refolding, oxidation, or reduction steps during its purification.
Using surface plasmon resonance technology and competitive binding assays, we have shown that
Affitoxin binds specifically to HER2 with nanomolar affinity. We have also observed a high correlation between HER2 expression and retention of
Affitoxin bound to the cell surface.
Affitoxin binding and internalization is followed by Pseudomonas exotoxin A activity domain-mediated ADP-ribosylation of translation elongation factor 2 and, consequently, inhibition of protein synthesis as shown by protein expression analysis of HER2-positive cells treated with
Affitoxin. Measured IC50 value for HER2-negative cells MDA-MB468 (65+/-2.63 pM) was more than 20 times higher than the value for low HER2 level-expressing MCF7 cells (2.56+/-0.1 pM), and almost 3 orders of magnitude higher for its HER2-overexpressing derivative MCF7/HER2 (62.7+/-5.9 fM).
These studies suggest that
Affitoxin is an attractive PE38-based candidate for treatment of HER2-positive tumors.
__________________
Jackie07
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