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Wednesday, September 17, 2014

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Molecular robots can help researchers build more targeted therapeutics

Public release date: 28-Jul-2013
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Contact: Phyllis Fisher
phyllis.fisher@gmail.com
212-606-1724
Hospital for Special Surgery 

Molecular robots can help researchers build more targeted therapeutics

Study demonstrates technique to create better anti-cancer agents, arthritis drugs, and more

 IMAGE: "This is a proof of concept study using human cells, " said Sergei Rudchenko, Ph.D., director of flow cytometry at Hospital for Special Surgery in New York City and a senior...
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Many drugs such as agents for cancer or autoimmune diseases have nasty side effects because while they kill disease-causing cells, they also affect healthy cells. Now a new study has demonstrated a technique for developing more targeted drugs, by using molecular "robots" to hone in on more specific populations of cells.

"This is a proof of concept study using human cells," said Sergei Rudchenko, Ph.D., director of flow cytometry at Hospital for Special Surgery (HSS) in New York City and a senior author of the study. "The next step is to conduct tests in a mouse model of leukemia." The study, a collaboration between researchers from HSS and Columbia University, is in Advance Online Publication on the website of Nature Nanotechnology.

All cells have many receptors on their cell surface. When antibodies or drugs bind to a receptor, a cell is triggered to perform a certain function or behave in a certain manner. Drugs can target disease-causing cells by binding to a receptor, but in some cases, disease-causing cells do not have unique receptors and therefore drugs also bind to healthy cells and cause "off-target" side effects.

Rituximab (Rituxan, Genentech), for example, is used to treat rheumatoid arthritis, non-Hodgkin's lymphoma and chronic lymphocytic leukemia by docking on CD20 receptors of aberrant cells that are causing the diseases. However, certain immune cells also have CD20 receptors and thus the drug can interfere with a person's ability to mount a fight against infection.

In the new study, scientists have designed molecular robots that can identify multiple receptors on cell surfaces, thereby effectively labeling more specific subpopulations of cells. The molecular robots, called molecular automata, are composed of a mixture of antibodies and short strands of DNA. These short DNA strands, otherwise called oligonucleotides, can be manufactured by researchers in a laboratory with any user-specified sequence.

The researchers conducted their experiments using white blood cells. All white blood cells have CD45 receptors, but only subsets have other receptors such as CD20, CD3, and CD8. In one experiment, HSS researchers created three different molecular robots. Each one had an antibody component of either CD45, CD3 or CD8 and a DNA component. The DNA components of the robots were created to have a high affinity to the DNA components of another robot. DNA can be thought of as a double stranded helix that contains two strands of coded letters, and certain strands have a higher affinity to particular strands than others.
The researchers mixed human blood from healthy donors with their molecular robots. When a molecular robot carrying a CD45 antibody latched on to a CD45 receptor of a cell and a molecular robot carrying a CD3 antibody latched on to a different welcoming receptor of the same cell, the close proximity of the DNA strands from the two robots triggered a cascade reaction, where certain strands were ripped apart and more complementary strands joined together. The result was a unique, single strand of DNA that was displayed only on a cell that had these two receptors.

The addition of a molecular robot carrying a CD8 antibody docking on a cell that expressed CD45, CD3 and CD8 caused this strand to grow. The researchers also showed that the strand could be programmed to fluoresce when exposed to a solution. The robots can essentially label a subpopulation of cells allowing for more targeted therapy. The researchers say the use of increasing numbers of molecular robots will allow researchers to zero in on more and more specific subsets of cell populations. In computer programming language, the molecular robots are performing what is known as an "if yes, then proceed to X function."

"The automata trigger the growth of more strongly complementary oligonucleotides. The reactions occur fast. In about 15 minutes, we can label cells," said Maria Rudchenko, M.S., the first author of the paper and a research associate at Hospital for Special Surgery. In terms of clinical applications, researchers could either label cells that they want to target or cells they want to avoid.

"This is a proof of concept study that it works in human whole blood," said Dr. Rudchenko. "The next step is to test it in animals."

If molecular robots work in studies with mice and eventually human clinical trials, the researches say there are a wide range of possible clinical applications. For example, cancer patients could benefit from more targeted chemotherapeutics. Drugs for autoimmune diseases could be more specifically tailored to impact disease-causing autoimmune cells and not the immune cells that people need to fight infection.
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The study was funded, in part, by the National Institutes of Health, National Science Foundation, and the Lymphoma and Leukemia Foundation.

Other researchers involved with the study are Alesia Dechkovskaia from Hospital for Special Surgery, and Steven Taylor, Ph.D., Payal Pallavi, B.A., Safana Khan, Vincent Butler, M.D., and Milan Stojanovic, Ph.D., from Columbia University. Dr. Stojanovich is also a senior author.

About Hospital for Special Surgery
Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopedics, No. 4 in rheumatology and No. 5 in geriatrics by U.S. News & World Report (2013-14), and is the first hospital in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center three consecutive times. HSS has one of the lowest infection rates in the country. From 2007 to 2012, HSS has been a recipient of the HealthGrades Joint Replacement Excellence Award. HSS is a member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College and as such all Hospital for Special Surgery medical staff are faculty of Weill Cornell. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at http://www.hss.edu.

For more information contact:
Phyllis Fisher
212-606-1197
Phyllis.Fisher@gmail.com

Tuesday, September 16, 2014

Who inspired you to join pancreatic cancer fight?


My wife inspired me to join the fight against pancreatic cancer.

Pancreatic Cancer in the News

Medscape
UK's NICE: No to Nab-Paclitaxel for Pancreatic Cancer
"Unfortunately, the development of new treatments for pancreatic cancer has been very limited in recent years," commented Sir Andrew Dillon, NICE ...
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Felling auctions purple trailer to benefit pancreatic research
Felling Trailers is conducting its second online auction of a FT-3 drop deck utility trailer to benefit cancer research and support. Felling Trailers wants ...
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Plymouth Herald
Famous victims of disease
Patrick Swayze was diagnosed with Stage 4 pancreatic cancer in January 2008. The Dirty Dancing star had numerous operations but died on ...
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Byetta Lawsuit News: New Order Issued in Federal Incretin Mimetics Litigation, Bernstein Liebhard ...
The Firm is evaluating Byetta lawsuits on behalf of individuals who developed pancreatitis, pancreatic cancer or thyroid cancer allegedly due to their ...
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BLOGS
The 5th Annual Run-n-Gun For a Cure Event
Pancreatic Cancer The highlight of our evening was that Jack Andraka and Kiera Chirdon were able to attend our dinner event. Jack is the 2012 Intel ...
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WEB
Pancreatic Cancer Action Network Accepting Applications for 2015 Pathway to Leadership Grant
The Pancreatic Cancer Action Network, in partnership with the American Association for Cancer Research, is accepting applications for its 2015 ...
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Sunday, September 14, 2014

Walking to cure pancreatic cancer -- Join us in Denver on November 2nd, 2014

Event Logo

You can help make a difference!  Join the fight and walk for a cure!  Register today!


Pre-Registration Fee $50
Walk-In Registration Fee $60
Registration 9:00 am
Walk starts at 10:30 am

Join us on Sunday, November 2, 2014 at Sloan's Lake Park, Denver, CO. Pancreatic Cancer Research Events are a great way to increase funding for research and raise awareness for pancreatic cancer. Lustgarten Foundation Events serve as a wonderful celebration of the progress being made in the fight against this disease, and your important participation provides hope for the future.


Saturday, September 13, 2014

Halozyme's PEGPH20 Program In Metastatic Pancreatic Cancer Receives Fast Track Designation

SAN DIEGO, Sept. 3, 2014 /PRNewswire/ -- Halozyme Therapeutics, Inc. HALO, -0.53% today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Halozyme's program investigating PEGPH20 (PEGylated recombinant human hyaluronidase) in combination with gemcitabine and nab-paclitaxel for the treatment of patients with metastatic pancreatic cancer to demonstrate an improvement in overall survival. The Fast Track designation process was developed by the FDA to facilitate the development, and expedite the review of drugs to treat serious or life-threatening diseases and address unmet medical needs.

"The FDA's Fast Track designation for our PEGPH20 program in pancreatic cancer underscores the significant need for new treatment options for pancreatic cancer patients with advanced disease," stated Dr. Helen Torley, President and Chief Executive Officer. "We look forward to continuing to work with the FDA on this program to explore whether patients with metastatic pancreatic cancer can benefit from this therapy."

The Fast Track Drug Development Program was established under the FDA Modernization Act of 1997. The program is designed to facilitate frequent interactions with the FDA review team to expedite clinical development and submission of a Biologic License Application (BLA) for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs. Specifically, Fast Track designation facilitates meetings to discuss all aspects of development to support approval. It also provides the opportunity to submit sections of a BLA on a rolling basis as data become available. This permits the FDA to review portions of the BLA as they are received instead of waiting for the entire BLA submission.

About HalozymeHalozyme Therapeutics is a biopharmaceutical company dedicated to developing and commercializing innovative products that advance patient care. With a diversified portfolio of enzymes that target the extracellular matrix, the Company's research focuses primarily on a family of human enzymes, known as hyaluronidases, which increase the dispersion and absorption of biologics, drugs and fluids. Halozyme's pipeline addresses therapeutic areas, including oncology, diabetes and dermatology that have significant unmet medical need today. The Company markets Hylenex® recombinant (hyaluronidase human injection) and has partnerships with Roche, Pfizer and Baxter. Halozyme is headquartered in San Diego, CA. For more information on how we are innovating, please visit our corporate website at www.halozyme.com.

Safe Harbor Statement In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, statements concerning future actions relating to the development of PEGPH20 and the possibility that PEGPH20 may be used to address pancreatic cancer) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are typically, but not always, identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including delays in completion of clinical trials and other development activities, the possibility of safety events, unexpected expenditures and costs, unexpected results or delays in regulatory review, regulatory approval requirements, unexpected adverse events and competitive conditions. These and other factors that may result in differences are discussed in greater detail in Halozyme's Quarterly

Report on Form 10-Q filed with the Securities and Exchange Commission on August 11, 2014.

Investor Contact:Schond Greenway
Halozyme Therapeutics
858-704-8352
ir@halozyme.com
Media Contact:Susan Neath Francis
212-301-7182
sfrancis@wcgworld.com
Logo - http://photos.prnewswire.com/prnh/20100302/LA63139LOGO
SOURCE Halozyme Therapeutics, Inc.



http://www.marketwatch.com/story/halozymes-pegph20-program-in-metastatic-pancreatic-cancer-receives-fast-track-designation-2014-09-03

Friday, September 12, 2014

Lustgarten Needs Volunteers!

Volunteers Needed for National

Has pancreatic cancer affected your family?  Do you want to help find a cure?  Then the Denver Lustgarten Pancreatic Cancer Walk need your help!  

Here's your opportunity to give to the cause with your time and energy.  Whether you're looking to join the Walk Committee or the want to be a "day of volunteer" call us! We need your help!

Please reach out to Sharon Golob!