GAITHERSBURG, Md., Nov. 20 /PRNewswire/ -- Panacea Pharmaceuticals, Inc.
announced the presentation of three papers covering diagnostic and therapeutic
applications of the Company's human aspartyl (asparaginyl) beta-hydroxylase or
HAAH Oncology Program. The papers were presented at the "Molecular Targets and
Cancer Therapeutics" meeting that was sponsored jointly by the American
Association for Cancer Research (AACR), the European Organization for Research
and Treatment of Cancer (EORTC), and The National Cancer Institute (NCI) in
Boston, Massachusetts.
"We continue to advance our understanding of the role of HAAH diagnostics
in cancer detection, diagnosis, prognosis, treatment selection, and follow-
up," stated Kasra Ghanbari, President of the Company. "We are currently
exploring applications and expanding the scope of studies to better define the
utility of these tools for cancer management."
The first presentation, entitled, "HAAH as a Biomarker for Pancreatic
Adenocarcinoma Using IHC, qRT-PCR, and ELISA," was presented by Audrey Anne
Vasauskas, Project Leader for Methods Development at the Company. Ms.
Vasauskas presented data evaluating HAAH as a biomarker for pancreatic
adenocarcinoma utilizing IHC and ELISA as well as qRT-PCR to measure ASPH, the
gene that encodes for HAAH. Utilizing the serum-based ELISA assay, HAAH was
detected in the serum of 18 out of 20 pancreatic cancer samples. A panel of
ten tissue specimens from patients with pancreatic adenocarcinoma along with
three samples of adjacent tissue were analyzed for HAAH expression by IHC. Two
of the adjacent non-cancer specimens displayed features of chronic
pancreatitis. All 9 pancreatic adenocarcinoma specimens were positive, 1
mucinous cystadenocarcinoma specimen was negative, and the adjacent normal
specimen was negative as were the two chronic pancreatitis specimens. Total
mRNA was isolated from the same pancreatic specimens used for IHC and the
level of gene expression was determined using the qRT-PCR assay. Detection of
ASPH message correlated with a diagnosis of cancer, but not with tumor stage.
ASPH message also was higher in moderately differentiated than well-
differentiated specimens. Low message levels were found in normal,
pancreatitis and mucinous adenocarcinoma specimens, in agreement with the
results of the IHC assay. Taken together, these data suggest that measurement
of HAAH levels may have utility for confirming the presence of cancer in
individuals at risk for pancreatic adenocarcinoma and for predicting the
clinical course of the disease.
The second presentation, entitled, "Anti-Proliferative and Anti-Metastatic
Activities of Monoclonal Antibodies to Human Aspartyl (Asparaginyl) Beta-
Hydroxylase," was presented by Angela H. Finney, Research Scientist for HAAH
Oncology Program at the Company. Ms. Finney presented data on the use of two
monoclonal antibodies, FB50 and 15C7, to identify tumor cell lines that
express HAAH and to inhibit cancer cell proliferation, motility and
invasiveness. Both FB50 and 15C7 detected high level expression of HAAH in a
lung carcinoma cell line (H460), a glioblastoma cell line (U-87 MG) and a
hepatocellular carcinoma cell line (FOCUS) by both western blotting and flow
cytometry. A breast carcinoma cell line (MCF-7) exhibited very low to
undetectable levels of HAAH. The level of HAAH expression correlated with the
migratory potential of the cells (H460 > U-87> FOCUS). MCF-7 cells were
essentially non-motile. Antibody effects on cellular motility, invasiveness
and proliferation were determined. 15C7 and FB50 inhibited motility of H460
cells in a dose-dependent fashion with an IC50 of approximately 50nM for both
antibodies. The motility of FOCUS and U-87 cells was also inhibited by anti-
HAAH antibodies with IC50 values of 120nM and 300nM, respectively. Cellular
invasion through an in vitro mimic of the extracellular matrix was inhibited
by the anti-HAAH antibodies at concentrations comparable to those effective at
inhibition of motility. Cellular proliferation of all cell lines, including
the MCF-7, was inhibited by both anti-HAAH antibodies. The potent inhibition
of both cellular proliferation and motility suggests the potential of these
antibodies to act as both anti-proliferative as well as anti-metastatic
agents.
The third presentation, entitled, "Isolation and Engineering of
Biologically Active Human Single-Chain Antibody Fragments (ScFvs) Against
Human Aspartyl (Asparaginyl) Beta-Hydroxylase," was presented by Andy Yeung of
the Massachusetts Institute of Technology, a collaborating institution. Mr.
Yeung presented data on the use of yeast surface display technology to
engineer proteins by directed evolution. In this method, mutated proteins are
displayed on the yeast surface and those displaying the improved mutants are
screened and isolated using flow activated cell sorter (FACS) or magnetic
activated cell sorter (MACS). Recently, the MIT group constructed and
expressed a non-immune library of 109 human antibody fragments (scFvs) on
yeast surface. Novel scFvs against different targets such as EGF and EGFR have
been isolated from this naive human scFv library. Utilizing a recombinant form
of the entire extracellular domain of HAAH, the group screened the human scFv
library to isolate novel scFvs targeting different epitopes of HAAH. After 6
rounds of screening, 16 unique clones were identified, of which 8 bound to the
catalytic domain of HAAH. These catalytic domain binders were expressed in
soluble form and analyzed for both binding and biological activities. One of
these soluble antibodies showed binding to both full length and catalytic
domain of HAAH by ELISA and was capable of inhibiting 90% of cell motility.
Currently, this clone is being matured to increase its affinity against HAAH
using the yeast surface display technology. These affinity-matured human
antibody fragments may have utility for cancer diagnostics or therapeutics.
Background on HAAH Oncology Program
The Company's HAAH Oncology Program is based on the enzyme human aspartyl
(asparaginyl) beta-hydroxylase (HAAH).
HAAH over-expression has been detected in primary tumor tissue of more
than twenty tumor types tested to date, including cancers of the pancreas,
breast, ovary, liver, colon, prostate, lung, brain, and bile duct. HAAH over-
expression has been detected in 99% of tumor specimens (greater than 1000)
tested to date and has not been detected in normal or adjacent non-affected
tissue.
Recent findings in preclinical studies have indicated that over-expression
of HAAH is sufficient to induce cellular transformation, to increase cell
motility and invasiveness, and to establish tumor formation in animals. Even
partial inhibition of HAAH expression has been shown to have a beneficial
effect on tumor cells, causing them to revert to a more normal phenotype as
measured by the inhibition of growth, motility, and invasiveness. HAAH is
over-expressed on the surface of cancer cells, potentially facilitating
detection, drug delivery, and enzyme inhibition.
Panacea signed a Collaboration and License Agreement with MedImmune, Inc.
in early 2002 to discover, develop, and commercialize therapeutic agents for
the prevention or treatment of human disease based on Panacea's HAAH
technology or its pathways. Panacea has retained all rights to the development
of diagnostic products based on HAAH.
About Panacea Pharmaceuticals, Inc.
Panacea Pharmaceuticals, Inc. is an emerging biopharmaceutical company
focused on utilizing functional genomics and proteomics to develop
therapeutics and diagnostics for diseases with substantial unmet clinical
need. The Company's product development focus is on novel proteins and
biochemical pathways related to cellular regulation and cell cycle
abnormalities in oncology as well as both acute and chronic neurodegenerative
conditions such as hypoxia-induced cognitive impairment, Parkinson's disease,
and Alzheimer's disease. The Company's wholly owned subsidiary, Proteus
Diagnostics, Inc., will be developing in vitro diagnostics including
pharmacogenomic and pharmacoproteomic tools for cancer detection, diagnosis,
prognosis, treatment selection, and follow-up.
More information is available at http://www.PanaceaPharma.com and
http://www.ProteusDx.com.
Except for historical information presented in this press release, matters
discussed herein may constitute "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995. Forward-
looking statements are based on the opinions and estimates of management only
as of the date of this release and are subject to certain risks and
uncertainties that could cause actual results to differ materially from any
future results, performance, or achievements expressed or implied by such
statements. Factors that might cause such a difference include, but are not
limited to, uncertainties related to our access to capital, the progress,
costs, and results of any clinical trials undertaken by us, progress of our
research and development projects, and uncertainties related to whether our
product candidates would ultimately achieve commercial success. We do not
undertake any obligation to update publicly any forward-looking statement,
whether as a result of new information, future events, or otherwise unless
required by law.
Contact:
Panacea Pharmaceuticals, Inc.
Kasra Ghanbari, President
Phone 240-243-8000 x108; FAX 240-465-0450
Kasra@PanaceaPharma.com
SOURCE Panacea Pharmaceuticals, Inc.
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Related links:
http://www.panaceapharma.com
http://www.ProteusDx.com
CONTACT:
Kasra Ghanbari, President, Panacea
Pharmaceuticals, Inc., +1-240-243-8000, ext. 108, fax:
+1-240-465-0450, or Kasra@PanaceaPharma.com
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