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:6/23/2017)... , ... June 23, 2017 , ... Everybody has their ... while others prefer to read it, and some people don't like it at all. ... Here's what they found: , Erotic literature can give readers a taste of their ...
(Date:6/23/2017)... ... June 23, 2017 , ... 21 Middle East and South Asia Leaders Selected ... from government, business and civil society in 11 countries across the Middle East and ... in a transformative exchange of knowledge and ideas with the leading minds in their ...
(Date:6/23/2017)... ... 23, 2017 , ... Ulster University, Magee Campus in Northern Ireland is hosting ... pm to present to graduate students exciting new and innovative hope research based on ... by The Health Improvement Service of the Western Health & Social Care Trust (WHSCT) ...
(Date:6/23/2017)... ... June 23, 2017 , ... Moore Insurance, ... area with access to asset protection and financial planning services, is teaming up ... improving the lives of children with cancer and other chronic diseases. , The ...
(Date:6/22/2017)... ... June 22, 2017 , ... ... from the American Heart Association (AHA) to launch a Rheumatic Heart Disease Center, ... prevention and diagnosis of rheumatic heart disease (RHD) in high-risk, financially disadvantaged countries ...
Breaking Medicine News(10 mins):
(Date:6/16/2017)... , June 16, 2017  Exactly 50 years ago ... off what later became known as the San Francisco "Summer ... ) is unveiling two radical innovations in strategic market research ... This announcement marks the beginning of Northern Light,s "Summer of ... ...
(Date:6/12/2017)... , June 12, 2017 Kineta, Inc., a biotechnology ... Kineta Vice President of R&D and Head of ... Pandemic Preparedness for the Northwest and Beyond meeting ... on June 14, 2017 from 8:30-10:30 AM PDT at the ... Dr. Bedard will be joined by other ...
(Date:6/8/2017)... MAITLAND, Fla. , June 8, 2017  Less ... ransomware attack that hit more than 200,000 companies, including hospital ... is being heralded as one of the largest online ... technology in the healthcare market, it is imperative that ... can protect their data from this — and many ...
Breaking Medicine Technology: