Nanoparticle Targets Tumor Infiltrating Immune Cells
5 years, 2 months ago
10392
0
Posted on Jan 21, 2019, 8 p.m.
Vanderbilt University bioengineers have made a breakthrough in penetrating cells inside tumors and activating a switch that tells them to start fighting, as published in the journal Nature Nanotechnology.
Scientist recently won a Nobel Prize for work unleashing the ability for the immune system to eliminate tumor cells making great strides in immunotherapy’s fight against cancer. This approach keeps cancer cells from shutting off the immune system’s T-cells before they can fight against the tumors, and is just one way to use the body’s defenses. The Vanderbilt team has built on this breakthrough to come forth with another by designing a nanoscale particle which is capable of penetrating tumor infiltrating immune cells and activates them to start fighting.
Tumors have evolved many ways to evade detection from the immune system, our goal was to rearm the immune system with tools needed to destroy cancer cells, by developing a nanoparticle to find tumors and deliver specific molecules produced naturally by the body to fight off cancer, says John T. Wilson.
CGAMP molecules are being used as the nanoparticle’s primary way to switch on the stimulator of interferon genes pathway which is a natural mechanism used by the body to mount immune responses against viruses, bacteria, or clear out malignant cells. The nanoparticle delivers cGAMP in a manner to jump start immune responses inside tumors which results in generation of killer T-cells that can destroy tumors from the inside out, and improve responses to checkpoint blockade.
The team focused on melanoma and their findings indicate this method could impact treatment of many other forms of cancer such as head, neck, breast, lung, kidney, colorectal, and neuroblastoma.
The process began with trying to develop nanoparticles using smart polymers which respond to changes in PH that are engineered to enhance potency of cGAMP; after 20+ iterations one was found capable of delivering cGAMP to activate STING efficiently in mouse immune cells, then in mouse tumors, and eventually in human tissue samples. According to Daniel Shae PhD, this work is really encouraging as it has demonstrated this technology may have success in patients.
Materials provided by Vanderbilt University.
Note: Content may be edited for style and length.
Journal Reference:
Daniel Shae, Kyle W. Becker, Plamen Christov, Dong Soo Yun, Abigail K. R. Lytton-Jean, Sema Sevimli, Manuel Ascano, Mark Kelley, Douglas B. Johnson, Justin M. Balko, John T. Wilson. Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy. Nature Nanotechnology, 2019; DOI: 10.1038/s41565-018-0342-5
