Artificial cells as a novel approach to gene therapy - Artificial Cells, Cell Engineering and Therapy - page 263

true with regard to those antibodies generated by recombinant means, as
illustrated with the recent success of Herceptin TM for treatment of breast cancer
and Avastin TM for treatment of colorectal cancer. In the case of Herceptin TM in
the United Kingdom, of the 35 000 women diagnosed with breast cancer each
year, about 20 000 will be suitable for HER2 testing. From this group of 20 000
women, about 5000 women may benefit from Herceptin TM , although only
approximately 1000 lives each year would be saved ± all at an annual cost of
about £100 million (www.medicalnewstoday.com, 2005). Artificial cells
delivering recombinant forms of this antibody may be a more cost-effective
approach. There have been some studies in the encapsulation of hybridomas to
deliver antibodies in an animal model that were successful in long-term systemic
antibody delivery (Pelegrin et al., 1998; Dautzenberg et al., 1999; Haas et al.,
1999; Orive et al., 2001). Thus, delivery of antibodies with microencapsulation
could become an important tool as more antibodies become available for a
growing list of potential tumor antigens.
10.5.4 Anti-angiogenic therapy
Angiogenesis, the propagation of new blood vessels from pre-existing vascula-
ture, is required for tumor growth and metastasis (Folkman, 1971). With respect
to artificial cells for cancer gene therapy, anti-angiogenic therapy is a new
approach that complements this platform technology well in several ways.
Firstly, endothelial cells undergoing angiogenesis are dissimilar to those that are
quiescent at the molecular level. For example, proliferating endothelial cells
display certain extracellular markers such as a plasma membrane bound ATP
synthase (Moser et al., 1999) or integrin v 3 (Tarui et al., 2001). Although
most prevalent in development, apart from wound healing and menstruation,
endothelial cells in a healthy adult are typically quiescent with only approxi-
mately 1 in 10 000 cells undergoing proliferation (Hobson and Denekamp,
1984). Indeed, cancer probably represents the most prevalent source of patho-
logical angiogenesis. This means that targeting angiogenesis for cancer therapy
would probably be well tolerated. Secondly, many of the anti-angiogenic factors
available are recombinant proteins that encapsulated cells could be genetically
engineered to produce. Such factors include recombinant antibodies to proangio-
genic factors, signaling molecules as well as peptide fragments (Cao, 1998).
Currently only a few anti-angiogenic agents have been approved for cancer
therapy. These include Avastin TM , a VEGF-neutralizing monoclonal antibody
(McCarthy, 2003); Endostar (Endostatin) recently approved in China as a
benchmark treatment for all cancers ± to be administered repeatedly and poten-
tially indefinitely. As described above, delivery of antibodies from artificial
cells is a viable strategy and may be more cost effective than the traditional
bolus administration of the purified product, particularly for treatments
involving recombinant proteins to be delivered for an indefinite period.