New nanoparticle developed for intravenous cancer immunotherapy

Date:
September 30, 2021
Source:
University of Michigan
Summary:
Cancer immunotherapy seeks to turn 'cold' tumors into 'hot' tumors -
- those that respond to immunotherapy -- by awakening and enlisting
the body's own immune system.



FULL STORY ========================================================================== Cancer immunotherapy seeks to turn "cold" tumors into "hot" tumors --
those that respond to immunotherapy -- by awakening and enlisting the
body's own immune system.


========================================================================== Unfortunately, few people benefit from the most common form of
immunotherapy, called immune checkpoint inhibitors, and scientists
are actively seeking new and safe molecules called agonists to augment
the body's immune response. One promising drug in clinical trials is
the STING agonist. STING is a protein essential to the immune response
against infection as well as cancer.

In searching for molecules that would augment the STING pathway, a team
of scientists at the University of Michigan School of Pharmacy and the
Rogel Cancer Center looked to nutritional metal ions, which we absorb
from food, and are important for immune regulation.

They found that adding the nutritional metal ion manganese to STING
agonists boosted STING's tumor-fighting capability up to 77-fold, compared
to STING agonists used alone, said James Moon, the J.G. Searle Professor
of Pharmaceutical Sciences and professor of biomedical engineering.

When researchers added the manganese ions to STING agonists, they formed
nano- sized crystals, which significantly increased cellular uptake of
STING agonists and STING activation by immune cells. To develop a STING
agonist for intravenous administration, the researchers coated these nanocrystals with a lipid layer (similar to those found in mRNA COVID19 vaccines), resulting in a nanoparticle system called CMP.

Most STING agonists must be delivered directly into the tumor, but this
isn't suitable for metastatic cancers, a major cause of mortality. Even
with intratumoral injections, conventional STING agonists are challenged
by limited clinical response.



==========================================================================
"CMP significantly increases cellular uptake of STING agonists,
and together with manganese, CMP triggers robust STING activation,
turns a cold tumor into hot tumor, and eliminates cancer, including
those that are completely resistant to immune checkpoint inhibitors,
the most widely used cancer immunotherapy," said Xiaoqi "Kevin" Sun,
a U-M graduate student in pharmacy and first author on the paper.

Moon said it's the first time that nanoparticles delivering STING agonists
and metal ions have been developed for intravenous cancer immunotherapy,
and this could open new doors for cancer immunotherapy treatments.

The team demonstrated the tumor-fighting effects of CMP in various tumors, including colon carcinoma, melanoma, and head and neck cancer.

Most head and neck cancers don't respond well to immune checkpoint
inhibitors.

To model this deadly disease, the team developed a head and neck cancer
model that was completely resistant to immune checkpoint inhibitors,
said study senior co-author Yu Leo Lei, U-M associate professor of
dentistry. The model, called NOOC1, bears over 90% similarity in
mutational signatures to smoking- associated human cancers.

"In the head and neck cancer tumor, CMP administered intravenously
eradicated those tumors in 75% of mice," Lei said. "In contrast,
conventional STING agonists had minimal anti-tumor effects and all animals succumbed to tumor growth." The study team is currently working to test
the safety and efficacy of CMP in large animals.

"We anticipate that we will be able to initiate a phase I clinical study
to examine the efficacy of CMP in cancer patients in the near future,"
Moon said.

========================================================================== Story Source: Materials provided by University_of_Michigan. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiaoqi Sun, Yu Zhang, Jiaqian Li, Kyung Soo Park, Kai Han,
Xingwu Zhou,
Yao Xu, Jutaek Nam, Jin Xu, Xiaoyue Shi, Lei Wei, Yu Leo Lei &
James J.

Moon. Amplifying STING activation by cyclic dinucleotide-manganese
particles for local and systemic cancer metalloimmunotherapy. Nature
Nanotechnology, 2021 DOI: 10.1038/s41565-021-00962-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210930125016.htm

--- up 4 weeks, 8 hours, 25 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)