Scripps Research Institute Scientists Develop Powerful New Meod for Finding erapeutic Antibodies
23/05/2013
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
04/08/2024
Dalet Appoints Santiago Solanas as CEO to Lead Next Era of Growth and Innovation
Dalet, a leading technology and service provider for media-rich organizations, is excited to announce Santiago Solanas as its new Chief Executive Officer (CEO)....
03/06/2024
Dalet and Veritone Reach Agreement to Distribute, Transact and Monetize Media Archives
Dalet, a leading technology and service provider for media-rich organizations, a...
21/05/2024
AMG Chooses Brightline For Frame' Ad Format
LOS ANGELES Allen Media Group (AMG) has launched an instream Frame ad for advertisers on its The Weather Channel, Local Now and HBCU Go connected TV (CTV) app...
21/05/2024
Wisconsin TV Stations Change Call Signs, Channel Numbers
MILWAUKEE Low power TV (LPTV) station operator Roseland Broadcasting has changed the call sign and the operating channel number of its two Wisconsin stations in...
21/05/2024
U.S. FAST Channels Hit Record Numbers
NEW YORK Despite rapid growth in recent years and worries that the FAST channel market may be reaching saturation, a new report from FASTMaster shows that the t...
21/05/2024
Cineverse to Offer Remastered HD, 4K Episodes of the Bob Rosss 'Joy of Painting
LOS ANGELES Hoping to build on the success of The Bob Ross Channel, Cineverse ha...
21/05/2024
DLT Launches 80's Sitcom Flashback Fast Channel
NEW YORK DLT Entertainment has announced the launch of 80's Sitcom Flashback, a FAST Channel exclusively curated to celebrate the comedies that dominated pr...
21/05/2024
SPL Media House Selects Grass Valley's AMPP
MONTREAL Grass Valley has announced that SPL Media House (SPL MH) in Riyadh, Saudi Arabia has deployed Grass Valley's AMPP SaaS Platform deployment in the r...
21/05/2024
Christ Church Deploys Pliant Technologies Intercoms at West Monroe Location
WEST MONROE, La. Pliant Technologies has announced that Christ Church, which has campuses in West Monroe, Ruston, and Sterlington, has deployed its CrewCom Wire...
21/05/2024
Hollyland Announces Pyro S, a New Wireless 4K Video Monitoring System for Filmmakers
Hollyland Announces Pyro S, a New Wireless 4K Video Monitoring System for Filmma...
21/05/2024
Avid Unveils Revolutionary Post-Production Micro-Certifications with New Learning Partner, Post Super
Avid Unveils Revolutionary Post-Production Micro-Certifications with New Learnin...
21/05/2024
MIX's Carpool Casanova Announces Spirit Award Finalists for Season 3
MIX 101.5's Carpool Casanova will wrap season three this Friday, May 24, 2024, but his final location has yet to be determined. The ultimate Spirit Award W...
21/05/2024
Dr. Ray Seol Awarded Grant for Creative Individuals from Mass Cultural Council
Dr. Ray Seol Awarded Grant for Creative Individuals from Mass Cultural Council The grant will expand his Seu Aprendiz project designed to help individuals bui...
21/05/2024
May 20, 2024
New method to reveal what drives brain diseases Scripps Research scientists develop CRISPR screen technology to determine disease mechanism from tissues with ac...
20/05/2024
Masters of Reinvention commissioned for Yesterday & UKTV Play
22nd May 2024 UKTV has commissioned Masters of Reinvention (6x60) for its leading factual channel Yesterday and free streaming service UKTV Play, to be produced...
20/05/2024
The Tuba Thieves Asks What It Means to Listen
PARK CITY, UTAH - JANUARY 22: The cast and crew of The Tuba Thieves pose during the 2023 Sundance Film Festival The Tuba Thieves premiere at Prospector Squa...
20/05/2024
Spotify CLASSICS: The 100 Greatest Hip-Hop Songs of the Streaming Era
Reviews by Carl Chery, Kemet High, and Adrian Covert In February, we launched Spotify CLASSICS-our first-ever program to celebrate catalog music. Our inaugur...
20/05/2024
Hamish Blake to host Alone Australia Season 2: The Reunion on 29 May
Hamish Blake to host Alone Australia Season 2: The Reunion on 29 May 20 May, 2024 Media releases As the season nears its end, SBS's hit series cements ...
20/05/2024
Poolside Gossip
Created by showrunner Abe Sylvia, the Apple TV+ comedic drama Palm Royale navigates the tale of one womans ambitious journey to make it amongst the upper crust,...
20/05/2024
SPL Media House selects Grass Valley AMPP SaaS Platform to Distribute Live Saudi Pro League Football Matches Globally
AMPP's cloud enabled rapid deployment of live production workflows with dist...
20/05/2024
EditShare celebrates anniversaries at CABSAT with innovations, integrations and implementations
EditShare Celebrates Anniversaries at CABSAT with Innovations, Integrations and ...
20/05/2024
Sony-Apollo's Bid for Paramount Gets Serious
A bid from Sony Pictures Entertainment and Apollo Global Management to acquire Paramount gained steam late last week, according to a report in the New York Time...
20/05/2024
Vizrt Unveils Viz Libro 8.3 With New Social Media Cropping Function
BERGEN, Norway Vizrt has released Viz Libero 8.3 with the announcement that its latest software version enables users to crop video to various aspect ratios fro...
20/05/2024
The Vampire Next Door Created with Pocket Cinema Camera 6K and DaVinci Resolve
The Vampire Next Door Created with Pocket Cinema Camera 6K and DaVinci Resolve Brie Clayton May 20, 2024 0 Comments Blackmagic Design today announced ...
20/05/2024
Tom Wills To Retire After Nearly 50 Years at WJXT Jacksonville
Tom Wills, long-running anchor at WJXT Jacksonville, Florida, has announced his retirement. He started at WJXT in 1975 and has anchored early-evening news for o...
20/05/2024
AMC Networks Promotes Emily Gotto to Senior VP at Shudder
AMC Networks said it promoted Emily Gotto to senior VP of acquisition and production for Shudder, the company's horror-themed streaming service....
20/05/2024
Paramount Names Jonathan Bingaman President, Domestic Multi-Platform Licensing & Distribution
Jonathan Bingaman has been named president, domestic multi-platform licensing & ...
20/05/2024
DLT Entertainment Gets FAST Laughs With 80's Sitcom Flashback Channel
Producer and distributor DLT Entertainment said it launched a free ad-supported streaming television (FAST) channel called 80's Sitcom Flashback....
20/05/2024
Zeam Media Names Sandie Trombert CMO
Zeam Media said it hired Sandie Trombert as chief marketing officer....
20/05/2024
Meet the VFX producer
Angus Berryman, VFX producer at UNIT studio tells TVBEurope how perseverance paid off as his career progressed By Matthew Corrigan Published: May 20, 2024 ...
20/05/2024
Sony signs NDA with Paramount Global but is reticent about earlier plan
The New York Times said the move was a significant step forward in their effort to court Paramount By Matthew Corrigan Published: May 20, 2024 The New Yor...
20/05/2024
CBC HR Team Getting Ballpark Staff Ready to Play Ball
A pair of stalwart members of the Capitol Broadcasting's dream team have been getting the company's two Coastal Plain League teams ready to launch their...
20/05/2024
Tonight on Scandal: Dintle's work life suffers as she struggles to hold it all together
Tonight on Scandal: Dintle's work life suffers as she struggles to hold it a...
20/05/2024
Every Company to Be an Intelligence Manufacturer,' Declares NVIDIA CEO Jensen Huang at Dell Technologies World
AI heralds a new era of innovation for every business in every industry, NVIDIA ...
20/05/2024
VEON's Banglalink and Robi Axiata Partner to Explore Network Sharing to Expand 4G Access in Bangladesh
20 May 2024 VEON's Banglalink and Robi Axiata Partner to Explore Network Sh...
20/05/2024
Queensland Rugby League Taps Layercake, DoubleTake Sports, Enveu for OTT Tech Stack
Queensland Rugby League Taps Layercake, DoubleTake Sports, Enveu for OTT Tech St...
20/05/2024
Maglia Rosa: EMG Italy on Managing the Logistics and Technicalities of the 2024 Giro d'Italia
Maglia rosa: EMG Italy on managing the logistics and technicalities of the 2024 ...
20/05/2024
Next-Generation Technology: EMG Italy Completes Extensive San Siro Infrastructure Overhaul
Next-generation technology: EMG Italy completes extensive San Siro infrastructur...
20/05/2024
Broadcast Innovation in India: How Augmented Reality, Data-Driven Graphics Production Are Changing Everything
Broadcast Innovation in India: How Augmented Reality, Data-Driven Graphics Produ...
20/05/2024
A Year-Long Planning Process: How Game Presentation of Super Bowl LVIII Influences Next Year's Party in New Orleans
A Year-Long Planning Process: How Game Presentation of Super Bowl LVIII Influenc...
20/05/2024
SVG College Summit 2024: Clemson's Kyle Coulter Breaks Down the Tigers' Fourth Quarter Hype Video
SVG College Summit 2024: Clemson's Kyle Coulter Breaks Down the Tigers' ...
20/05/2024
HARMAN Professional Solutions Appoints Algam Ibrica as the Official Distribution Partner in Spain
May 20, 2024 LONDON-HARMAN Professional Solutions, the global leader in audio, ...
20/05/2024
RIP: Two deaths' on Shaka ILembe' production
RIP: Two deaths' on Shaka ILembe' productionTwo people, who are part of the Shaka Ilembe' production set to return for a second season, have repo...
20/05/2024
Gangsterism in movies and television: Wees geskool'
Gangsterism in movies and television: Wees geskool'Gangsterism has been portrayed in movies and television: but have you ever seen these films and televisi...
20/05/2024
School project features Die Antwoord' [Watch]
School project features Die Antwoord' [Watch]School projects are difficult. However, this student took some inspiration from the controversial band Die An...
20/05/2024
Tonight on Skeem Saam: Ntswaki sneaks Toby into the house but sadly for her, Leeto arrives unannounced
Tonight on Skeem Saam: Ntswaki sneaks Toby into the house but sadly for her, Lee...
20/05/2024
Thales and Nokia partner to deliver seamless renewal to London Underground
Facebook Twitter LinkedIn Thales, with its transmission network technology partner, Nokia, has been selected by Transport for London (TfL) to deliver an i...
20/05/2024
May 17, 2024
Scripps Research chemists develop new method for making gamma chiral centers on simple carboxylic acids C-H activation-based method should speed drug molecule ...
20/05/2024
First European Election Major TV Debate this Monday Night on Upfront with Katie Hannon
As part of RT 's extensive coverage in the run up to the European Parliament...
19/05/2024
TV Techs Weekly Product Wrap-Up
Missed any of our product coverage during your busy week? The TV Tech weekly product and services news wrap-up provides links to all of our coverage from May 13...