Navigation Links
Fox Chase clinical trial tests first of its kind antibody
Date:6/4/2010

CHICAGO, IL. (June 7, 2010)Patients with HER2-positive cancers can have dramatic responses to HER2-targeted drugs but eventually develop resistance to the agents. With that problem in mind, Fox Chase Cancer Center researchers are testing a novel type of antibody called MM-111 in patients with HER2-positive disease who have progressed on standard therapy.

Unlike natural antibodies, which have two arms that recognize the same antigen, the new MM-111 antibody has one arm that binds the HER2 receptor on the cell surface and a second arm that binds the HER3 receptor and blocks signaling through HER3.

"This is the first-in-human bi-specific antibody that targets the HER2/HER3 pathway," says Crystal Denlinger, M.D., a medical oncologist who is leading the phase I/II trial at Fox Chase. "It uses the HER2 target to deliver a punch to the HER3 pathway." Denlinger will present the phase I/II study design and background data at the 46th Annual Meeting of the American Society of Clinical Oncology on Monday, June 7.

Scientists have recently found that HER3 (also called ErbB3) signaling is an important therapeutic target in HER2-positive cancers. HER3 is the preferred binding partner for the HER2 receptor and together they promote tumor growth. In tumors that have become resistant to HER2-targeted drugs, the HER3 receptor may become highly active and appears to contribute to the resistance.

"With MM-111, we now have the technology and ability to exploit this pathway and provide an additional therapeutic target within the HER2 pathway," Denlinger says.

Enrollment in the phase I portion of the trial is complete with 11 advanced breast cancer patients and one HER2-positive gastric cancer patient. The final safety analysis for the phase I portion is on-going, and the team anticipates beginning enrollment of patients in the phase II portion of the trial later this summer. Advanced breast cancer patients with HER2-positive disease who have progressed on standard therapy and have adequate performance status, bone marrow reserve, and organ function will be eligible for the phase II trial.

"I am really excited about this drug," Denlinger says. "It is a fascinating mechanism, certainly a novel mechanism, and I think the concept of using HER2 as a target to bring a therapeutic intervention to HER3 makes a lot of sense. Many HER2-positive patients develop resistance to their HER2-directed therapies, so if we can find an alternative means to block that pathway by targeting HER3 that would be a clinically meaningful step forward for the HER2 population in breast cancer and in other HER2-positive cancers."

The trial is sponsored by Merrimack Pharmaceuticals, Inc. (Cambridge, Mass.), which is developing the antibody.

The general concept behind the new drug was first developed at Fox Chase in collaboration with researchers at the University of California, San Francisco. Both institutions joined to license the intellectual property for the bispecific antibody to Merrimack, which further refined the antibody and made it more suitable for use as a drug in humans.

The origin of the double-headed antibody has its roots in a conversation between Louis Weiner, M.D., then-chair of medical oncology at Fox Chase, and Greg Adams, Ph.D., an antibody engineer and Co-Leader of Fox Chase's Molecular and Translational Medicine Program. Weiner and Adams took the concept of an anti-ErbB2/ErbB3 bispecific antibody to their long-term collaborator James Marks, M.D., Ph.D., of the University of California, San Francisco. The Adams lab used recombinant DNA technology to engineer the ErbB2 and ErbB3 targets which the Marks lab then used to isolate the antibodies that the Adams lab used to engineer the prototype bispecific antibodies. The exquisite ability of these prototype bispecific antibodies to target and treat breast cancer cells was then determined in the laboratory by Matthew Robinson, Ph.D., a Fox Chase associate member.

After licensing the intellectual property, Merrimack scientists further refined the concept to create a new drug. Its antibody arms bind more tightly to their targets and its linker chain is derived from a human protein, which allows the drug to survive in the bloodstream longer. According to Merrimack, MM-111 is the first bispecific antibody binding two different receptors on the same cell to enter clinical development.


'/>"/>

Contact: Diana Quattrone
Diana.Quattrone@fccc.edu
215-728-7784
Fox Chase Cancer Center
Source:Eurekalert

Related medicine news :

1. MedQuist Agrees to Purchase Domestic Assets of Spheris
2. Transparency Should Not Be a Luxury; It Is a Matter of Life and Death: What Purchasers and Consumers Can Do
3. Men Likely to Research a Purchase, Not Ask for Advice
4. Kensey Nash Announces 400,000 Share Stock Repurchase Program
5. Web's Newest, Sub-1000 Range of Hot Tubs Now Available For Purchase Online!
6. Securities Class Action Filed by Shepherd, Finkelman, Miller & Shah, LLP on Behalf of Hemispherx Biopharma Securities Purchasers Between February 18, 2009 and November 2, 2009
7. Medizone International, Inc. Approves Repurchase of Global Marketing Rights
8. Smart Balance Authorizes Stock Repurchase Program
9. IQS Testing Purchased by The Compliance Management Group
10. Cardiome Pharma Corp. Permitting Automatic Securities Disposition and Purchase Plans
11. Will Your Purchase of an Electric Mobility Scooter Lead to a Comedy of Errors?
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 26, 2016 , ... On June 10-11, 2016, A ... 2016 Cereal Festival and World’s Longest Breakfast Table in Battle Creek, MI, where the ... history as home to some of the world’s leading providers of cereal and other ...
(Date:6/26/2016)... ... 2016 , ... PawPaws brand pet supplements owned by Whole Health ... the health of felines. The formula is all-natural and is made from Chinese herbs ... Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract and Rehmannia ...
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery ... of Mohs Surgery and to Dr. Russell Peckham for medical and surgical dermatology. , ... for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey ...
(Date:6/25/2016)... ... , ... "With 30 hand-drawn hand gesture animations, FCPX users can easily customize ... Pixel Film Studios. , ProHand Cartoon’s package transforms over 1,300 hand-drawn pictures into ... Simply select a ProHand generator and drag it above media or text in the ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... -- MedSource announced today that it has selected Datatrial,s ... choice.  This latest decision demonstrates MedSource,s commitment to ... by offering a state-of-the-art electronic data capture (EDC) ... the EDC platform of choice in exchange for ... long been a preferred EDC platform by our ...
(Date:6/23/2016)... -- Research and Markets has announced the ... (Organic Chemical (Sugar, Petrochemical, Glycerin), Inorganic Chemical), Functionality (Filler, ... Global Forecast to 2021" report to their offering. ... pharmaceutical excipients market is projected to reach USD 8.1 ... the forecast period 2016 to 2021. ...
(Date:6/23/2016)... June 23, 2016 Research and Markets ... Medical Market Analysis 2016 - Forecast to 2022" report ... The report contains up to date financial data derived from ... of major trends with potential impact on the market during ... market segmentation which comprises of sub markets, regional and country ...
Breaking Medicine Technology: