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advancing targeted cancer therapy
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is a biotechnology company committed to discovering,
developing, and commercializing novel, targeted therapies for
gliomas, metastatic brain tumors, and other aggressive cancers
with limited treatment options. Our talented team is dedicated
to expediting the research and approval processes necessary to
bring promising new treatment options – as well as renewed
hope – to millions of patients who need them.
has been used to describe
the selective binding of a drug to tumor cells, usually on a molecular
level. One significant advantage that a targeted therapy has over
most traditional therapies is the focus of therapeutic effect
on the cancer cell, which reduces toxicity to non-cancerous cells
(i.e., less collateral damage to non-target cells). The potential
for greater are efficacy with significantly less toxicity than
traditional chemotherapies has created great interest in developing
targeted therapies. A variety of protein, lipid, and carbohydrate
molecules have been explored as potential candidates for cancer
therapies.
TransMolecular,
Inc. is currently developing a targeted approach to treating cancer
using a synthetic version of chlorotoxin (TM-601), a 36-amino
acid peptide derived from scorpion venom (Figure 1). TM-601 has
shown no significant toxicities in pre-clinical animal and human
clinical studies.
Studies have demonstrated that TM-601 has a high
affinity for tumor cells (Figure 2), and a low affinity for normal,
healthy cells. For more information about histological studies
demonstrating the tumor cell specificity of TM-601, click
here.
The effect of TM-601 coupled with I, a radioisotope,
is currently being explored in high-grade glioma and metastatic
solid tumors. TransMolecular, Inc. is also planning to explore
the effects of TM-601 alone or coupled with other chemotherapeutic
agents in treating a variety of different cancers.
Figure 1. Scorpion and 3-D Structure and
Amino Acid Sequence of Chlorotoxin (TM-601).
Above, left: Giant Yellow Israeli scorpion which
produces venom from which chlorotoxin peptide sequence was originally
derived. Above, middle: 3-D structure of chlorotoxin determined
by NM. Above, right: Amino acid sequence of chlorotoxin.
Figure 2. Binding of TM-601 to Glioblastoma
Tissue
A. No Peptide
B. Non-specific Biotinylated Peptide
Gliomas are tumors that affect the glial cells in the
central nervous systems. Glial cells are non-neuronal cells that
have various roles (depending on type and location) in supporting
neuronal function.
Gliomas are a relatively rare form of brain tumor.
Primary CNS tumors occur in approximately 6.4% per 100,000 people;
51% of these are glioma tumors.
There are several different types of gliomas, named
according to the types of glial cell affected. The most common
gliomas that affect the brain are:
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Astrocytomas |
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Oligodendrocytomas |
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Ependymomas |
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Mixed gliomas |
Gliomas may range in severity from slow growing
and benign to highly invasive and malignant. The most severe form
of glioma is glioblastoma multiforme, a highly
aggressive tumor that spreads rapidly throughout the brain. Glioblastomas
are generally resistant to currently available treatments; the
average length of survival following diagnosis is one year. The
very poor prognosis and poor response to treatment underscore
the need for effective new therapies for this type of brain tumor.
For a brief overview of information gliomas and glioblastoma,
you can visit the disease
information section of this website. For more comprehensive
information about gliomas and glioblastomas, you can visit the
additional resources
section of the website. There you will find a list of websites
with links to professional organizations that provide in-depth
information about gliomas and other brain tumors.
TransMolecular has developed a comprehensive clinical
trial program to evaluate the efficacy and safety of radiolabeled
 I-TM-601
and unlabeled TM-601 in treatment of
patients with glioblastoma multiforme and other refractory, high-grade
gliomas. The program also includes early clinical trials in other
tumor types via IV injection of radiolabeled TM-601. I-TM-601
was approved as an investigational drug in April, 2002, was granted
orphan status for patients with high-grade glioma, and has received
fast-track designation.
A phase I/II study and the first “dose-escalating”
sequence* of a phase II study have been completed in recurrent,
late-stage glioma patients. A larger-scale, second sequence of
the phase II high-grade glioma study is ongoing. Imaging studies
of IV administered I-TM-601
in patients with multiple primary and metastatic tumor types are
also being conducted.
In addition, Transmolecular recently gained FDA
approval of an IND to investigate unlabeled TM601 based on evidence
that IV-administered, unlabeled TM-601 has antitumor effects of
its own, potentially due to antiangiogenic activity. TransMolecular
is planning to conduct a clinical study to evaluate the effects
of unlabeled TM-601 alone in the treatment of high-grade glioma
that is expected to begin enrolling patients in early 2008.
More information about TransMolecular
clinical trials currently recruiting patients can also be found
at the following websites:
* The completed dose-escalating study, which
included 15 patients and was designed to evaluate safe dosage
ranges for I-TM-601,
was the first sequence of a larger ongoing phase II clinical trial
evaluating the efficacy and safety of I-TM-601
in patients with high-grade glioma.
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