New screening method identifies potential anticancer compounds that reawaken T cells The technique may be useful in developing new combination-immunotherapy regimens against cancers and persistent infections.
December 03, 2019
LA JOLLA, CA Scientists at Scripps Research have developed a method for rapidly discovering potential cancer-treating compounds that work by resurrecting anti-tumor activity in immune cells called T cells.
Cancerous tumors often thrive because they render T cells dysfunctional or exhausted. The new method uncovers medicinal compounds that can restore the function of these T cells, making cancers vulnerable to them again.
The approach, described in a study published in Cell Reports, may also help restore T-cell responses to persistent infections from viruses or other pathogens. It therefore should speed the development of new cancer and infectious-disease immunotherapies, including those that can be combined with existing immunotherapy drugs to enhance their effects. The scientists demonstrated the potential utility of the approach by using it to rapidly screen a collection of more than 12,000 drug compounds uncovering 19 that can reawaken exhausted T cells.
This new screening method should be particularly useful because we can use it not only to identify compounds that restore needed function to exhausted T cells, but also to quickly analyze these T cells to determine how these compounds work on them, says senior author Michael Oldstone, MD, Professor Emeritus in the Department of Immunology and Microbiology at Scripps Research.
The new screening system and to some extent, the wider field of cancer immunotherapy is based in part on research over the past several decades by Oldstone's laboratory and several former lab members including Rafi Ahmed, David Brooks, and John Teijaro, along with other scientists that have conducted animal-based research on how the immune system responds to lymphocytic choriomeningitis virus (LCMV).
A unique variant of LCMV known as clone 13 establishes a persistent infection by exhausting the virus-specific T cells that are required to clear the infection. It does this by boosting signals through T-cell receptors such as PD-1 and IL-10. The discovery that LCMV clone 13 can survive by switching off anti-LCMV T cells was quickly followed by the recognition that cancers often persist using the same trick.
Immunotherapies that block signaling from PD-1 or similarly acting receptors to restore T cells' anti-cancer responses are among the most powerful cancer medicines available today. These therapies save many patients who in the past had seemingly untreatable tumors. But because treatment with these drugs typically works well for only a few cancers, including melanoma and less often on other cancers scientists suspect that cancers usually hijack multiple inhibitory T-cell pathways. This suggests that a combination of immunotherapies directed to different molecular pathways could be more effective than the current therapy.
The idea now is to develop more immunotherapy drugs and find the best combinations of them, Oldstone says.
A promising hit
The new screening system is designed to enable scientists to swiftly find such drugs in this case, pharmacologically active small-molecule compounds that might work better than, or augment, the current injectable antibody immunotherapies now available.
The system uses T cells that have been exhausted by LCMV clone 13 and detects signs of renewed activity in these cells when a tested compound works to reawaken them. An advantage of the new screening system is that it is specific and highly automated; thus, thousands of compounds can be tested within days, with the hits verified in experiments involving mice.
Oldstone and colleagues applied the new screening system to a drug repurposing library of more than 12,000 compounds that either are FDA-approved or have been tested as potential drugs. They quickly identified 19 hits compounds that, at modest doses, can effectively resurrect the activity of exhausted T cells.
One of these compounds, ingenol mebutate, is a plant-derived molecule that is already used in gel form (Picato) to treat actinic keratosis, a pre-cancerous skin condition. The researchers employed elements of their screening system to study the reactivated T cells and determined that ingenol mebutate restores function for these cells largely by activating signaling enzymes called protein kinase C enzymes, a known pathway of activity for this compound.
Co-first authors of the study, postdoctoral fellows Brett Marro, PhD and Jaroslav Zak, PhD, in the Department of Immunology and Microbiology, are currently collecting and exploring the therapeutic potential of other reported hits that may work in combination with treatments that block PD-1- and another T-cell-inhibitory receptor, CTLA-4. Indeed, one such hit in combination with antibody to PD-L1 is already undergoing evaluation in patients.
Oldstone notes that the new screening approach is flexible enough to adapt for finding compounds that have other effects on T-cells, such as reducing T-cell activity to treat autoimmune conditions.
Authors of the study, Discovery of Small Molecules for the Reversal of T Cell Exhaustion, also included Scripps Research scientists Reza Beheshti Zavareh, a postdoctoral fellow in the Lairson laboratory, and Luke Lairson, an associate professor in the Department of Chemistry.
Support for the research was provided by the National Institutes of Health (R01 AI099699, AI009484, AI123210 & AI118862, R21 AI141842).
Cancer Oldstone, Michael
Most recent headlines
02/01/2025
NextGen TV, aka ATSC 3.0, continued to advance in 2024, with some notable developments and renewed hopes that a deregulatory-minded Federal Communications Commi...
02/01/2025
Artificial intelligence is undoubtedly the hottest topic in the tech industry today, displaying all the excitement, apprehension and hype of the early days of t...
02/01/2025
STAMFORD, Conn. NBC Sports said 2024 was its best year in terms of ratings since 2016. Its success was fueled by the Paris Summer Olympics as well as its NFL co...
02/01/2025
MSG Networks has been dropped from Altice USA's Optimum-branded pay TV offerings after the operator and the regional sports provider were unable to reach a ...
02/01/2025
How color film and analog color TV works with bluescreen / chromakey
Graham Quince January 2, 2025
0 Comments
A deep dive into VFX History looking at ...
02/01/2025
Hulu Series Interior Chinatown Graded with DaVinci Resolve Studio
Brie Clayton January 2, 2025
0 Comments
Colorist Aidan Stanford delivers complex gra...
02/01/2025
Bulk Font Replacement in Premiere Pro
Andy Ford January 2, 2025
0 Comments
If you want to change the font of multiple text layers in Premiere Pro, the...
02/01/2025
Streaming media's impact on the media and entertainment industry continued to widen in 2024, as more sports rights moved to streaming platforms and the rapi...
02/01/2025
ATLANTA The board of directors for Gray Television Inc. has unanimously voted to change the company's name to Gray Media, Inc. effective Jan. 1....
02/01/2025
Official television and film archives exist to preserve the history and creativity of media. But even these formal institutions do not contain everything that h...
02/01/2025
Welsh succeeds Renard Jenkins, who has reached the end of his two-year tenure in the role
By Jenny Priestley
Published: January 2, 2025
Welsh succeeds Ren...
02/01/2025
Creator Economy Isn't Really Like Film/Show Entertainment
Andy Marken January 1, 2025
0 Comments
Come on Barry, you're good at this sort of s...
02/01/2025
Blackmagic Design Announces New Lower Price for Blackmagic Pocket Cinema Camera ...
02/01/2025
Hollywood Lighting Hacks: Big Looks, Tiny Budget
Sean Alami January 1, 2025
0 Comments
Discover how to create stunning Hollywood-style lighting using ...
02/01/2025
A fresh start to 2025 with new faces, familiar voices and plenty of Irish music ...
02/01/2025
GeForce NOW is kicking off 2025 by delivering 14 games to the cloud this month, with two available to stream this week so members can get started on their New Y...
01/01/2025
Marcy Lefkovitz, Dalet SVP product innovation, details the findings of the companys report into the future of newsrooms, including leveraging AI, optimising mul...
31/12/2024
Rashad Frett shares a moment with Michelle Satter at the 2023 Directors Lab. Pho...
31/12/2024
What's Ahead in 2025? OWC's Larry O'Connor Offers Some Bold Predicti...
31/12/2024
Blackmagic Design Announces New Features for Blackmagic Cloud
Brie Clayton December 31, 2024
0 Comments
New thumbnail icon view, clip metadata inspect...
31/12/2024
5 Features in DaVinci Resolve You're Not Using (But You Should Be)
Kasia Jarco December 31, 2024
0 Comments
In this video we are going to talk abo...
31/12/2024
Back to All News
NFL Christmas Day Games on Netflix Average Over 30 Million Global Viewers
Entertainment
31 December 2024
Global
Link copied to clipboard
...
31/12/2024
Back to All News
Squid Game' Season 2 Smashes Top 10 Records as Millions W...
30/12/2024
Leaving Thomson after 21 years, former Managing Director David Quin reflects on a career spent navigating the shifting sands of global media development. From r...
30/12/2024
[Pictured: a still from Love Lies Bleeding, one of the 100 Sundance-supported titles that opened to wider audiences in 2024]...
30/12/2024
Digital Domain Creates Groundbreaking VFX for Venom: The Last Dance, Bringing ...
30/12/2024
Internet Giant GMP Builds Tokyo Virtual Event Space with URSA Broadcast G2
Brie Clayton December 30, 2024
0 Comments
Blackmagic URSA Broadcast G2 and ...
30/12/2024
Renderboxes launches Photon, a no-compromise transportable high-performance work...
30/12/2024
Shinobi II Monitor Supports Canon, Sony, Nikon - Touch to Focus with New Feature...
30/12/2024
30 Dec 2024
In a Groundbreaking Agreement, VEON and Starlink to Bring Starlink ...
30/12/2024
The pace of technology innovation has accelerated in the past year, most dramati...
29/12/2024
Gyeongnam Culture and Arts Foundation (GCAF), an active promotor of cultural and artistic diversity, has chosen Ikegami UHK-X700 camera chains for integration i...
27/12/2024
After starting 2024 with hopes that the transition to streaming might finally produce a more stable, profitable businesses, the media and entertainment industry...
27/12/2024
Broadcasters ended the year with hopes and fears about how the federal government will regulate the TV industry in 2025. While the incoming Trump administration...
27/12/2024
NVIDIA's AI Podcast gives listeners the inside scoop on the ways AI is transforming nearly every industry. Since the show's debut in 2016, it's gar...
26/12/2024
Talking about artificial intelligence in 2024 is akin to talking about the internet in 1994 everyone's excited about it and thinks it will have an enormous ...
26/12/2024
Back to All News
Netflix NFL Christmas Gameday Reaches 65 Million US Viewers
Entertainment
26 December 2024
GlobalUnited States
Link copied to clipboard
U...
26/12/2024
Back to All News
Check Out All the Must-See Trailers From Netflix's NFL Chr...
26/12/2024
Back to All News
Beyonc Delivers Epic Gift of a Halftime Performance "Beyonc...
26/12/2024
Back to All News
Get in the Game With Squid Game' Season 2 Complete Coverage Guide
Entertainment
26 December 2024
Global
Link copied to clipboard
Are...
26/12/2024
This GFN Thursday wraps up another incredible year for cloud gaming. Take a look back at the top games and new features that made 2024 a standout for GeForce NO...
24/12/2024
The National Film and Video Foundation (NFVF) is calling for applications from South African film and television filmmakers to be part of the NFVF's delegat...
24/12/2024
WASHINGTON, D.C. The Federal Communications Commission Enforcement Bureau said Paramount Global is being fined $244,952 for violations of emergency alerting rul...
24/12/2024
NEW YORK Carnegie Hall's video-streaming channel, Carnegie Hall+, said it will celebrate the holiday season by offering a wide selection of holiday-themed o...
24/12/2024
LOS ANGELES PlayersTV, an athlete and fan-owned media company, has announced the acquisition of Cloud Media Center, an AI-driven sports adtech and media distrib...
24/12/2024
The Best Playlists of 2024 The top playlists we created in 2024, from dad rock to dembow.
By
Tara Bellucci
December 23, 2024
Image by Kelly Davidson
Tak...
24/12/2024
Editor's note: This post is part of the AI Decoded series, which demystifies AI by making the technology more accessible, and showcases new hardware, softwa...
23/12/2024
At IBC2024, Grass Valley CTO Ian Fletcher told attendees at GV Forum that broadcast is now an IT industry. During our discussions at the show, TVBEurope heard v...
23/12/2024
According to co-director Nick Park, the production team embraced technology to help create the iconic duos latest adventure
By Jenny Priestley
Published: Dec...
New screening method identifies potential anticancer compounds that reawaken T cells The technique may be useful in developing new combination-immunotherapy regimens against cancers and persistent infections.
