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Cancer immunotherapy is seeking to make "cold" tumors hot, those that are responding to immunotherapy, by stimulating and enlisting the own immune system of the body.

But according to a Phys.org report, few individuals are benefiting from the most common immunotherapy form, also known as immune checkpoint inhibitors, and researchers are actively searching for new and safe molecules also known as agonists to augment the immune response of the body.

One potential drug in clinical trials is the STING agonist. STING is a protein that's essential to the immune response combating infection and cancer.

In a quest for molecules that would enhance the STING pathway, a group of scientists at the University of Michigan School of Pharmacy and the Rogel Cancer Center investigated the nutritional metal ions, which are absorbed from food, and are essential for immune control.

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Science Times - Intravenous Cancer Immunotherapy: Scientists Develop New Nanoparticle, Protein Essential to Immune Response Against Infection
(Photo : National Institute of Standards and Technology on Wikimedia Commons)
Nanoparticles; Microscope Design


'STING' Agonists

These scientists discovered that adding the nutritional metal ion manganese to STING agonists augmented the tumor-combating capability of STING up to 77-fold, compared to the sole or exclusive use of STING. This was according to JG Searle Professor of Pharmaceutical Sciences and professor of biomedical engineering James Moon.

In their study published in Nano Technology, when the researchers added the manganese ions to STING agonists, they created nano-sized crystals, which substantially increased the STING agonist's cellular uptake, as well as the STING activation by immune cells.

The researchers coated the nanocrystals with a lipid layer akin to those that exist in mRNA COVID-19 vaccines, as described in the Centers for Disease Control and Prevention site, to develop a STING agonist for intravenous administration, leading to a nanoparticle system called CMP.

Most STIN agonists need to be delivered directly into the tumor, although this is not suitable for metastatic cancers, a primary cause of death.

Even with the so-called "intratumoral injections," conventional STING agonists are struggling because of limited clinical reactions.

CMP Nanoparticle System                                                                                    

According to Xiaoqi "Kevin Sun," a graduate student in pharmacy at UM, and the paper's first author, CMP substantially increases cellular uptake of STING agonists, and along with manganese, this nanoparticle system stimulates robust STING activation, transforms cold tumor into a hot one, and removes cancer which includes those that are totally resistant to immune checkpoint inhibitors which is the most extensively used cancer immunotherapy.

Meanwhile, Moon said that this is the first time nanoparticles that deliver STING agonist, as well as metal ions, have been made for intravenous cancer immunotherapy, "and this could open new doors for cancer immunotherapy treatments."

The scientists demonstrated the CMP's tumor-fighting effects in different tumors, which include colon carcinoma, melanoma, and head and neck cancer.

UM, associate professor of dentistry and the study's senior co-author Yu Leo Lei said most head and neck cancers do not react well to immune checkpoint inhibitors. To represent this fatal disease, the researchers developed a head and neck prototype that was entirely resistant to immune checkpoint inhibitors.

Safety and Efficacy in Large Animals

Meanwhile, the model also known as NOOC1 bears more than 90-percent resemblance in mutational signatures to smoking-linked human cancers.

Lei explained, in the head and neck cancer tumor, this nanoparticle system administered intravenously eliminated those tumors in more than 70 percent of rodent models.

On the contrary, conventional STING agonists had slight anti-tumor impacts and all animals died to the growth of the tumor.  

The research team is presently working to test CMP's safety and efficacy in large animals. Commenting on their finding, Moon said, they anticipate that they will be able to initiate Phase I clinical research to investigate the nanoparticle system's efficacy in cancer patients in the near future.

Related information about nanoparticles for drug delivery is shown on Entegris Particle Sizing's YouTube video below:

 

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