Highlights
- •Cancer stem cells appear to be directly targeted by use of an antibody against CD133.
- •An anti-CD133 targeted toxin, dCD133KDEL, shows promise for ovarian cancer therapy.
- •dCD133KDEL inhibits growth of ovarian carcinoma in vitro and in vivo in a mouse model.
Abstract
Objectives
While most women with ovarian cancer will achieve complete remission after treatment,
the majority will relapse within two years, highlighting the need for novel therapies.
Cancer stem cells (CSC) have been identified in ovarian cancer and most other carcinomas
as a small population of cells that can self-renew. CSC are more chemoresistant and
radio-resistant than the bulk tumor cells; it is likely that CSC are responsible for
relapse, the major problem in cancer treatment. CD133 has emerged as one of the most
promising markers for CSC in ovarian cancer. The hypothesis driving this study is
that despite their low numbers in ovarian cancer tumors, CSC can be eradicated using
CD133 targeted therapy and tumor growth can be inhibited.
Methods
Ovarian cancer cell lines were evaluated using flow cytometry for expression of CD133.
In vitro viability studies with an anti-CD133 targeted toxin were performed on one
of the cell lines, NIH:OVCAR5. The drug was tested in vivo using a stably transfected
luciferase-expressing NIH:OVCAR5 subline in nude mice, so that tumor growth could
be monitored by digital imaging in real time.
Results
Ovarian cancer cell lines showed 5.6% to 16.0% CD133 expression. dCD133KDEL inhibited
the in vitro growth of NIH:OVCAR5 cells. Despite low numbers of CD133-expressing cells
in the tumor population, intraperitoneal drug therapy caused a selective decrease
in tumor progression in intraperitoneal NIH:OVCAR5-luc tumors.
Conclusions
Directly targeting CSC that are a major cause of drug resistant tumor relapse with
an anti-CD133 targeted toxin shows promise for ovarian cancer therapy.
Abbreviations:
dCD133KDEL (deimmunized pseudomonas exotoxin fused to anti-CD133 scFv with a KDEL terminus), aa (amino acid), Ab (antibody), CD19 (cluster of differentiation 19), CD45 (cluster of differentiation 45), ER (endoplasmic reticulum), FITC (fluorescein isothiocyanate), KDEL (Lys-Asp-Glu-Leu), mAb (monoclonal antibody), PE (pseudomonas exotoxin), photons/s/cm2/sr (photons per second per square centimeter per steradian), scFv (recombinant single chain VH and VL domain)Keywords
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Article info
Publication history
Accepted:
May 17,
2013
Received:
February 13,
2013
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
