Polyglutamate Drug Delivery Technology
We are developing a new way to deliver cancer drugs more selectively
to tumor tissue to reduce the toxic side effects to normal organs and
tissues and to improve the anti-tumor activity of existing chemotherapy
agents.
Our technology links, or conjugates, cancer drugs to
biodegradable polymers, such as polyglutamate. Two of our product candidates,
XYOTAX™ (paclitaxel poliglumex) and CT-2106, use a unique biodegradable
protein polymer to deliver a taxane and a camptothecin, respectively,
to tumor tissue.
Polyglutamate Drug Delivery Mechanism of Action
Unlike vessels in healthy tissue, those in tumor tissue have openings
that make them porous to large molecules. XYOTAX leaks through the pores
in tumor blood vessels and due to the larger size of XYOTAX compared
to standard paclitaxel, it is preferentially trapped and distributed
to the tumor tissue. The polymer-linked cancer drugs are inactive while
circulating in the bloodstream, which may also lower toxicity compared
to the active cancer drug substance alone.
Once in the tumor tissue, the XYOTAX is taken up by
tumor cells through a cellular process called endocytosis. Because the
biopolymer XYOTAX is made of of biodigestible amino acids, it is slowly
metabolized by lysosomal enzymes (principally cathepsin B) inside the
lysosome in the tumor cell. Cathepsin B is up-regulated in the presence
of estrogen. This metabolism releases the active chemotherapy agent,
paclitaxel.
Possible Benefits of Polyglutamate Drug Delivery Technology
Based on preclinical animal studies and clinical trial data, we believe
that our polymer-cancer drug conjugates may be able to achieve a number
of benefits over existing chemotherapy drugs, including:
- Eliminates the need for toxic solubilizing agents
such as Cremophor/ethanol
- Eliminates the need for routine premedication
- Allows more drug to reach the tumor
- Decreases toxicity as a result of less active drug reaching normal
tissues
- Has potential to overcome resistance to the underlying chemotherapy
drug
- Similar or potentially better efficacy compared with standard treatments
History & Strategy of the Polyglutamate Technology
We licensed the worldwide exclusive rights to polyglutamate and related
polymers and their applications from PG-TXL Company in 1998. The technology
was originally developed at the M.D. Anderson Cancer Center. The initial
patent, which issued in November 1999, covers polyglutamate and related
polymers coupled with commonly used cancer drugs such as paclitaxel,
docetaxel, etoposide, teniposide, or camptothecins. The patented technology
covers formulations of polyglutamate-conjugated paclitaxel that also
include the use of human serum albumin and conjugation to epothilones.
Our strategy is to use this novel polymer technology to build a portfolio
of potentially safer and more effective versions of well-known anti-cancer
agents. We believe that our polymer drug development program may lower
the risks inherent in developing new drugs because we are linking polymers
to well defined and widely used chemotherapy drugs. We are initially
focusing our development efforts on applying polyglutamate to two of
the fastest growing classes of anticancer drugs, taxanes and camptothecins.
See our Clinical
Pipeline section for more information on the applications
of this technology - XYOTAX™ (paclitaxel poliglumex, CT-2103) and
CT-2106.
Posted March 4, 2008
Copyright © 2004-2008 Cell Therapeutics, Inc., Seattle,
WA, USA. All rights reserved. "Making cancer more treatable" is
a registered mark of CTI.
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