APR 03, 2018 12:59 PM PDT

New Compound Stimulates Cancer-Killing Invariant Natural Killer T Cells

WRITTEN BY: Kara Marker

Stimulating the immune system to better fight cancer and infections is now possible with a synthesized compound called AH10-7. Researchers from the University Connecticut show in their new study how this compound can stimulate powerful immune cells that kill tumors and attack pathogens: invariant natural killer T cells.

AH10-7 (yellow), an antigen-presenting cell (gray), and an invariant natural killer T cell (green and blue) that spark activation of iNKT cells. Credit: Jose Gascon/UConn

Invariant natural killer T (iNKT) cells are known to defend the body against all types of dangers: infection, cancer, and autoimmune diseases like multiple sclerosis and lupus. They are cells of the immune system that experts describe as living in a “poised effector state.” This means that after they are activated, iNKT cells quickly and continuously produce cytokines, chemical messengers of the immune system that either suppress or activate the inflammatory response.

Over the past several years, researchers have been studying ways to better stimulate iNKT cells to protect the body. Research has focused on both natural and synthetic forms of glycolipid ligands known as alpha-galactosylceramides (alpha-GalCers). Alpha-GalCers are particularly gifted at activating iNKT cells because they facilitate the interactions between antigen-presenting cells, like macrophages or dendritic cells, and iNKT cells so they can be activated to fight cancer or infections.

A compound called KRN7000 was the first ever synthesized alpha-GalCer to successfully stimulate iNKT cells. However, KRN7000 initiated the production of various cytokines, and researchers wanted a compound that selectively initiated the release of just one cytokine: Th1, which has anti-cancer activity.

In the new study, scientists introduce a compound called AH10-7. Unlike KRN7000, AH10-7 selectively activates Th1 cytokines, maximizing the benefit of using it to activate iNKT cells. AH10-7 was created with two major chemical modifications to make it so.

"We are providing protocols so that other scientists can rationally design related molecules that elicit desired responses from iNKT cells,” said chemist Jose Gascon.

Study leader Amy Howell has been investigating glycolipids and the human immune system for more than two decades. "One of the goals in this field has been to identify compounds that elicit a more biased or selective response from iNKT cells, and we were able to incorporate features in AH10-7 that did that," she said.

Howell and her team successfully tested AH10-7 in mice genetically altered to imitate the human iNKT response; the synthesized compound was at least as effective as KRN7000 at blocking the growth of melanoma.

Researchers also incorporated advanced structural and 3D computer modeling analysis to evaluate the components of AH10-7 that maximize its success with stimulating iNKT cells. By examining the molecular interaction between iNKT cell receptors and AH10-7, researchers saw several structural factors as providing a foundation for AH10-7’s unique ability to activate iNKT cells.

The present study was published in the journal Cell Chemical Biology.

Sources: Clinical Immunology, Nature Reviews Immunology, University of Connecticut

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
SEP 07, 2019
Immunology
SEP 07, 2019
A New Way To Fight Severe Peanut Allergies
Dr. Sandra Lin explains how SLIT is currently being used to treat allergies other than peanuts.    Over 1 million U.S. children have an allergy t...
OCT 19, 2019
Neuroscience
OCT 19, 2019
Autism May be Linked to an Immune Disorder
Until now, diagnosis for autism spectrum disorder have relied on behavioral assessments looking for symptoms including poor social and communication skills...
OCT 25, 2019
Drug Discovery & Development
OCT 25, 2019
Novel Therapeutic For Eradicating The Flu Virus
Public Health officials have long warned about pandemic pathogens flying fast around the world. One virus already spreads across the globe annually leading...
NOV 22, 2019
Immunology
NOV 22, 2019
Rogue Inflammation Activates Depression During Pregnancy
Unresolved inflammation in a pregnant woman’s body can lead to serious depression during and after pregnancy. A new study investigates the physiologi...
DEC 09, 2019
Immunology
DEC 09, 2019
Strep Throat Bacteria "Hides" from the Immune System
Group A Streptococcus (GAS), the bacterial species famous for sore throat infections, have a secret weapon for circumventing the immune response to bacteri...
DEC 31, 2019
Genetics & Genomics
DEC 31, 2019
Should the Scientist Behind World's First Gene Edited Babies be in Prison?
He Jiankui, the scientist behind the world’s first gene-edited babies in 2018, has been sentenced to three years in prison by Chinese authorities for...
Loading Comments...