Scripps Research Institute Scientists Develop Powerful New Method for Finding Therapeutic Antibodies As Proof of Principle, Technique Finds Antibody that Mimics Key Hormone for Blood Clotting
LA JOLLA, CA May 23, 2013 Scientists at The Scripps Research Institute (TSRI) have devised a powerful new technique for finding antibodies that have a desired biological effect. Antibodies, which can bind to billions of distinct targets, are already used in many of the world's best-selling medicines, diagnostics and laboratory reagents. The newly reported technique should greatly speed the process of discovering such products.
For the first time, we have a selection method whose power matches the vast diversity of the antibody repertoire, said Richard A. Lerner, the Lita Annenberg Hazen Professor of Immunochemistry at TSRI, member of the Department of Molecular Biology, and senior investigator for the new study, which appears in this week's issue of the Cell Press journal Chemistry and Biology.
As a demonstration of the potential of the new method, Lerner's team used it for the rapid discovery of an antibody that potently mimics thrombopoietin (TPO), a hormone that controls the production of clot-making platelets in blood.
The time from selection of the target through discovery of the antibody and completion of initial animal tests totaled only about five months, said Hongkai Zhang, a research associate in the Lerner laboratory who was first author of the study.
The antibody already has been licensed to a pharmaceutical company for further development.
Fast Selection
Antibodies are large, Y-shaped proteins produced by immune cells called B-cells in humans and many other animals. To cope with diverse and ever-changing threats from microorganisms, B-cells are able to rearrange and mutate a small set of their genes, so that collectively they can produce billions of distinct antibodies.
About two decades ago, Lerner's laboratory developed some of the first techniques for using B-cell gene-mixing to generate very large libraries of antibodies and swiftly determine which of these can bind to a desired target. Since then, Lerner and his colleagues have used these techniques to discover a number of therapeutic antibodies, including the anti-inflammatory antibody Humira , now one of the world's top-selling drugs.
In a major innovation reported last year, Lerner, Zhang and their colleagues developed a basic method for selecting antibodies that not only bind to a given target, such as a cell-surface receptor, but also have a desired biological function such as activating the receptor on mammalian cells. The researchers demonstrated the method by using it to find a potent antibody mimic, or agonist, of erythropoietin (EPO), a hormone that stimulates the production of red blood cells.
But this selection method has one drawback: it determines an antibody's ability to activate a desired biological pathway in a cell by measuring the resulting proliferation of that cell a slow and only narrowly applicable indicator.
We can use this cell-growth test to select for a lot of things including the discovery of antibodies with potential medical uses but Dr. Lerner and I wanted a more direct and generally applicable way of selecting for antibody function, Zhang said.
Two Million Test Cells Per Hour
The new method uses a sensitive reporter system in test cells, which gives off a fluorescent light signal as soon as an antibody succeeds in activating a receptor, or, in principle, any other targeted signaling pathway. The system also is set up so that each test cell produces a unique antibody, whose effect is confined to that cell. Each cell represents a separate assay, said Zhang.
With automation technology that can maintain millions of these cultured test cells, infect them with viral vectors that deliver antibody genes, and then detect the cells that fluoresce, the technique is capable of screening two million test cells per hour.
In the new study, the team proved the value of the new technique by using it to discover a potent agonist of TPO, a hormone that is essential for the proper clotting of blood in wound healing. TPO agonists can treat conditions involving a scarcity of blood platelets, for example as a result of cancer chemotherapy. However, drugs that structurally resemble the TPO hormone can be problematic; about 12 years ago a lab-grown, recombinant version of TPO failed in clinical trials when it was found to induce a deleterious anti-TPO antibody response. This left some patients with less TPO and a lowered platelet count the opposite of the intended treatment effect. Since then, other TPO agonists have been developed without this problem. But there's a real need for more TPO agonists that don't look like natural TPO, said Lerner.
The most powerful TPO agonist described in the study, antibody 3D9, performed much better in cell-culture tests that is, required a much smaller amount to activate the TPO receptor on test cells than TPO itself. At least part of the antibody's potency derives from its greater size and stability compared to a small molecule like TPO, which allows it to stay functional for a longer time.
The mouse TPO receptor is almost identical to human TPO receptor, so Zhang was able to test his antibody agonist in mice. A single, modest dose of 3D9 tripled platelet counts in mice over eight days a much more potent effect than that reported for recombinant TPO. This antibody is what I call a super-agonist, because it's more powerful than the authentic TPO agonist, said Lerner. It also looks superior to the other commercial TPO agonists, based on their reported potencies.
Lerner, Zhang and their colleagues are currently using the new selection method to find other useful antibodies for a variety of applications. One su
Most recent headlines
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
30/08/2025
WASHINGTON The Federal Communications Commission has adopted its FY 2025 Regulatory Fees Order that establishes the regulatory fee rates for the broadcast stati...
29/08/2025
Australian Red Cross and SBS launch training to help workplaces in the fight aga...
29/08/2025
The National Film and Video Foundation (NFVF), an agency of the Department of Sp...
29/08/2025
L3Harris Technologies has concentrated decades of expertise across the entire enterprise to develop affordable and reliable best-of-breed solutions to rapidly c...
29/08/2025
BURBANK, Calif. The CW Network and the Pac-12 Conference have announced a new media rights deal that will extend their broadcast partnership beginning with the ...
29/08/2025
NEW YORK Gracenote has released a new analysis of its global video dataset showing that the number of FAST channels grew nearly 14% from Q1 2025 and 76% since 2...
29/08/2025
SAN JOSE, Calif. Harmonic has announced a series of improvements to its live sports streaming solution that the company said will improve fan engagement, protec...
29/08/2025
NEW YORK and LOS ANGELES Fox Corp. and YouTube TV last night announced a renewal of the full portfolio of Fox networks, including Fox News Channel, Fox Business...
29/08/2025
Budapest, Hungary, August 2025 - The integration of Microsoft Teams Rooms (MTR) with Lightware's Taurus universal matrix switchers delivers a new level of f...
29/08/2025
Frequency, the engine behind many of the world's best-known streaming television channels, today announced it will launch Studio Live, a next-generation uni...
29/08/2025
In an era when AI and cyber resilience are essential, Scality will mark the 10th anniversary of Scality Day on October 16, 2025 in Paris. This flagship global e...
29/08/2025
Disguise's In-House Creative and Technical Teams Pre-Visualised, Programmed and Delivered Content for the Experience, All Powered by EX 3+
Technology solu...
29/08/2025
Disguise will be demonstrating the latest workflows for TV, film and live events on a number of partner booths at the show
Disguise, the industry-leading tech...
29/08/2025
STOCKHOLM, Sweden Accedo will showcase Accedo Compose, its AI agent-powered modular orchestration layer that assists streaming providers in transitioning client...
29/08/2025
LOS ANGELES Cineverse has announced that it is working with Xperi to bring four of its streaming channels to automobiles for the first time as part of the DTS A...
29/08/2025
DALLAS & ATLANTA Gray Media has announced an agreement with the sports streaming service Victory+ to simulcast 17 Dallas Stars NHL games in 15 television market...
29/08/2025
NEW YORK AND CULVER CITY Comcast NBCUniversal and Amazon have announced new and extended distribution agreements that will expand the content available on their...
29/08/2025
FOOTHILL RANCH, Calif. RED Digital Cinema will feature its Cine-Broadcast Module supporting live broadcast workflows during IBC2025, Sept. 12-15, at the RAI Ams...
29/08/2025
29 Aug 2025
Kyivstar Rings Opening Bell at Nasdaq Marking Landmark Listing and ...
29/08/2025
More than half of all NFL games live on Sky for the first timeFriday 29 August 2025
Sky Sports has announced a new three-year deal with the NFL, extending its ...
29/08/2025
Back to All News
RIV4LRIES: The Trailer of the New Series With Samuele Carrino ...
29/08/2025
Get ready for an inspiring and emotional insight into the world of competitive Irish dancing with My Story: Tomi Champion of the World airing on RT 2 this monda...
29/08/2025
RT has today announced that David McCullagh is to be the new presenter of RT Radio 1's flagship Today programme, which airs every weekday at 10am, replaci...
28/08/2025
By Kristin Feeley, Director, Documentary Film & Artist Programs
If you want to tell untold stories, if you want to give voice to the voiceless, you've got ...
28/08/2025
Directed by Steven Bognar and Julia Reichert, Sundance Institute-supported Amer...
28/08/2025
Corridos have been a cornerstone of M sica Mexicana for generations, telling stories rooted in everyday life. Now, a new chapter is taking shape: motivational c...
28/08/2025
Los corridos han sido un pilar de la M sica Mexicana durante generaciones, contando historias enraizadas en la vida cotidiana. Ahora, un nuevo cap tulo est tom...
28/08/2025
Earlier this month, we promised our Verano Forever party would bring the heat, a...
28/08/2025
L3Harris will provide the Polish F-16V fleet with the Viper Shield electronic warfare system as part of an upgrade program....
28/08/2025
Bilbao, August 26, 2025 - AgileTV, an international television and video technol...
28/08/2025
Ken Wilkinson is an Emmy Awards nominated New York audio engineer who specialises in production sound mixing for film, commercial, episodic and documentary work...
28/08/2025
NEW YORK FuboTV today announced that it will launch Fubo Sports, a skinny bundle that focuses on sports with a subscription price of $56 monthly....
28/08/2025
NEVADA City, Calif. At IBC2025, Sept. 12-15 at the RAI Amsterdam, Telestream will debut its new Global Ingest strategy, introducing a next-generation ingest arc...
28/08/2025
Dr. Rhoda Bernard Releases Groundbreaking Debut Book on Accessible Arts Educatio...
28/08/2025
TAG Video Systems, the leader in software-based IP end-to-end workflow monitoring, deep probing, and real-time visualization, has named Oliver Gappa as Sales Di...
28/08/2025
AI-based voice enhancement will be among a series of innovations making their IBC 2025 debut on the DHD stand B46 in Hall 8 at the RAI Amsterdam Convention Cent...
28/08/2025
Telef nica Servicios Audiovisuales (TSA), the leading system integrator and service provider in the media sector in Spain, with the support of Appear, the globa...
28/08/2025
To fully immerse sailing fans in the world's biggest offshore yacht race, production company, Optical Media turned to LiveU's On-site Production solutio...
28/08/2025
Working with Calrec on its most recent overhaul, radio and television broadcaster, WNED has migrated to a fully IP infrastructure with multiple Type R consoles,...
28/08/2025
Cleeng, the Subscriber Retention Management (SRM ) inventor, has unveiled Cleeng Pro, the first-ever direct-to-consumer (D2C) subscription management platform t...
28/08/2025
Zixi, the industry leader in live broadcast-quality video over IP, today announced that French media distribution platform OKAST has selected Zixi to enable rel...
28/08/2025
Solution offers a streamlined, speaker-free architecture to optimize integration with premium external loudspeakers and advanced loudness metering
Nixer Pro Au...
28/08/2025
Cinegy, the premier provider of software-defined television technology, has announced a strategic partnership with Vision One Touch Film Production Services L.L...
28/08/2025
Telestream, a global leader in media workflow technologies, will debut its new Global Ingest strategy at IBC2025, introducing a next-generation ingest architect...
28/08/2025
Tier 1 operator selects Broadpeak to power high-performance, unified CDN solution across Norway, Sweden and Finland
Broadpeak, a leader in streaming and moneti...
28/08/2025
Leading video software provider, Synamedia, today announced that 24 Frames Digital, one of India's leading live event streaming service providers, has chose...
28/08/2025
Meet VisualOn at IBC2025: See What's Next in AI-Powered Video Streaming Join VisualOn at IBC2025 and discover how our AI-driven Optimizer and advanced media...
Scripps Research Institute Scientists Develop Powerful New Method for Finding Therapeutic Antibodies As Proof of Principle, Technique Finds Antibody that Mimics Key Hormone for Blood Clotting
