Tuesday, December 5, 2023
SCIENMAG: Latest Science and Health News
No Result
View All Result
  • Login
  • HOME PAGE
  • BIOLOGY
  • CHEMISTRY AND PHYSICS
  • MEDICINE
    • Cancer
    • Infectious Emerging Diseases
  • SPACE
  • TECHNOLOGY
  • CONTACT US
  • HOME PAGE
  • BIOLOGY
  • CHEMISTRY AND PHYSICS
  • MEDICINE
    • Cancer
    • Infectious Emerging Diseases
  • SPACE
  • TECHNOLOGY
  • CONTACT US
No Result
View All Result
Scienmag - Latest science news from science magazine
No Result
View All Result
Home SCIENCE NEWS Medicine & Health

Moffitt researchers determine 1st crystal structure of LAG3

June 27, 2022
in Medicine & Health
0
Share on FacebookShare on Twitter

TAMPA, Fla. — Immune checkpoint inhibitors have revolutionized cancer care. The therapy works by preventing tumors from shutting down the immune response, which in turn allows T cells to kill cancer cells. Established checkpoint inhibitors target the proteins PD-1 and CTLA-4 and are used to treat a variety of solid tumor types, including melanoma and lung cancer. However, the U.S. Food and Drug Administration recently approved a new immune checkpoint inhibitor targeting the protein LAG3. This anti-LAG3 antibody, called relatlimab, was administered in combination with the anti-PD-1 antibody nivolumab to treat advanced melanoma.

LAG3 Crystal Structure

Credit: Moffitt Cancer Center

TAMPA, Fla. — Immune checkpoint inhibitors have revolutionized cancer care. The therapy works by preventing tumors from shutting down the immune response, which in turn allows T cells to kill cancer cells. Established checkpoint inhibitors target the proteins PD-1 and CTLA-4 and are used to treat a variety of solid tumor types, including melanoma and lung cancer. However, the U.S. Food and Drug Administration recently approved a new immune checkpoint inhibitor targeting the protein LAG3. This anti-LAG3 antibody, called relatlimab, was administered in combination with the anti-PD-1 antibody nivolumab to treat advanced melanoma.

Despite this therapeutic breakthrough, little has been known about the structure of the LAG3 protein. In the absence of a three-dimensional structure, LAG3-based drugs must be designed “in the dark” using inefficient screening methods. A team of Moffitt Cancer Center researchers has become the first in the world to visualize the molecular structure of the LAG3 protein. In a new article published in Nature Immunology, they describe the crystal structure of LAG3 and how it interacts with molecules produced by cancer cells.

“When I started my lab at Moffitt, I noticed a growing interest in LAG3 as an immunotherapy target. I was surprised at how little we knew about the LAG3 structure and its molecular mechanism, despite about 30 years of literature highlighting its role in the immune system,” said Vince Luca, Ph.D., assistant member of the Drug Discovery Department.

Luca and his team used X-ray crystallography to “see” the structure of the LAG3 protein at nearly atomic resolution. The researchers also mapped out the regions of LAG3 that bound to signaling molecules called FGL1 and MHCII and two different anti-LAG3 antibodies. From this information, they were able to determine which antibody binding sites were ideal to inhibit LAG3 activity.

Through their investigations, the researchers discovered how structural interactions of LAG3 and FGL1 inhibit T cell function. They found that binding of the two molecules causes LAG3 to cluster on the surface of T cells, which they hypothesize may contribute to the inhibitory activity of LAG3 by blocking the T cells from properly recognizing tumor cells.

These combined data reveal several important insights into the three-dimensional structure of LAG3 and how it interacts with other molecules, which may lead to better targeted therapeutic approaches in the future.

“Collectively, our structural, epitope mapping and functional studies provide an improved framework for understanding LAG3 molecular function. In the future, additional structures of LAG3 bound to ligands and antibodies will refine our knowledge of the LAG3 signaling axis to illuminate how extracellular binding events fine-tune LAG3-mediated changes in T cell activity. In turn, such structural insights should guide the development of maximally effective LAG3-based immunotherapies,” said Luca.

This study was supported by the National Institutes of Health (R35GM133482, P01AI120943, R01CA230610, P30CA076292), the V Foundation for Cancer Research and the Rita Allen Foundation Scholars Program.

In addition to their article, the journal also published a News & Views and Research Briefing on this research discovery.

About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 52 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 7,500 team members, Moffitt has an economic impact in the state of $2.4 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter, Instagram and YouTube. 

###



Journal

Nature Immunology

DOI

10.1038/s41590-022-01238-7

Method of Research

Experimental study

Subject of Research

Cells

Article Title

LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition

Article Publication Date

27-Jun-2022

Tags: 1stcrystaldetermineLAG3Moffittresearchersstructure
Share26Tweet16Share4ShareSendShare
  • Ryugu micrometeorites

    Meteorites likely source of nitrogen for early Earth

    69 shares
    Share 28 Tweet 17
  • New implants linked to less infection and better recovery from orthopedic surgery

    66 shares
    Share 26 Tweet 17
  • ‘Shocking’ discovery: Electricity from electric eels may transfer genetic material to nearby animals

    65 shares
    Share 26 Tweet 16
  • New study identifies the greatest threat to wildlife across North America and Canada: people

    65 shares
    Share 26 Tweet 16
  • Scientists build tiny biological robots from human cells

    68 shares
    Share 27 Tweet 17
  • Why have so many new diseases developed in the bagged salads sector?

    64 shares
    Share 26 Tweet 16
ADVERTISEMENT

About us

We bring you the latest science news from best research centers and universities around the world. Check our website.

Latest NEWS

Fungus from Arrakis: New species named after Dune’s giant worms

Scientists discover rare 6-planet system that moves in strange synchrony

Null results research now published by major behavioral medicine journal

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

Join 208 other subscribers

© 2023 Scienmag- Science Magazine: Latest Science News.

No Result
View All Result
  • HOME PAGE
  • BIOLOGY
  • CHEMISTRY AND PHYSICS
  • MEDICINE
    • Cancer
    • Infectious Emerging Diseases
  • SPACE
  • TECHNOLOGY
  • CONTACT US

© 2023 Scienmag- Science Magazine: Latest Science News.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In