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 17, 2019
Immunology
SEP 17, 2019
Unleashing the Immune System on Cancer
A team of international researchers has discovered that there may me a more from the immune system to aid in the battle against cancer...
SEP 17, 2019
Immunology
SEP 17, 2019
Anti-Inflammatory Meds without Side Effects, Please
Drugs such as ibuprofen or aspirin that relieve pain and lower fever are among the most frequently used drugs worldwide....
SEP 17, 2019
Immunology
SEP 17, 2019
Hay Fever? Mind your food!
For some, Spring means the return of itchy eyes and runny noses. Pollen is to blame for hay fever, but is it also causing food allergies?...
SEP 17, 2019
Cancer
SEP 17, 2019
Widely Prescribed Breast Cancer Medication Promotes Metastasis
The primary goals of metastatic breast cancer treatment are to ensure that the patient has the longest survival possible while experiencing the highes...
SEP 17, 2019
Cell & Molecular Biology
SEP 17, 2019
Understanding and Treating the Mechanisms That Drive Rheumatoid Arthritis
In RA, cells of the immune system mistakenly attack the joints, and cause the painful inflammation that is a hallmark of the disease....
SEP 17, 2019
Cardiology
SEP 17, 2019
Opioid Addiction Comes With Increased Risk Of Infection
Public health officials have put decades of work into the battle against infectious diseases. Now, this progress is at risk of being dismantled. A recent s...
Loading Comments...