A nanoparticle and inhibitor trigger the immune system, outsmarting brain cancer

Scientists at the University of Michigan were optimistic when they found a small molecule that blocked a key pathway in brain tumors. The problem was how to get the drug into the brain.

The results were even better than expected because the teams fabricated a nanoparticle to contain the inhibitor.

The potential new approach could not only treat the brain, but also eliminate the cancer in mouse models, as the drug successfully turned on the immune system to eliminate the cancer, and the process triggered immune memory so that a reintroduced tumor was also eliminated.

No one could get this molecule into the brain. It is a huge milestone. The outcomes for patients with glioma have not improved over the last 30 years, according to Maria G. Castro, the R.C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Castro is the senior author of the study.

Despite survival gains in many cancer types, glioma remains challenging, with only 5% of patients living five years after their diagnosis, according to study author Pedro R. Lowenstein.

The environment inside the tumor suppresses the immune system, making new immune-based therapies useless. It becomes more difficult to deliver effective treatments to these tumors because of the challenge of passing the blood brain barrier.

The lab saw an opportunity. The glioma cells release a cytokine that builds up a shield around the immune system, preventing it from firing up against the invading tumor, which is why the small molecule inhibitor is developed to block it. In mouse models of glioma, researchers showed that the binding of the CXCR12 with immune-suppressive myeloid cells was prevented by the AMD3100. The immune system can attack the tumors by disarming these cells.

There was trouble getting to the tumor. The drug didn't travel well through the bloodstream and it didn't pass the blood brain barrier, which is important for getting drugs into the brain.

The U-M College of Engineering and the Castro-Lowenstein lab collaborated to create a solution to help the drug pass through the bloodstream.

Castro was connected with Anuska V. Andjelkovic, M.D., professor of pathology and research professor of neurosurgery at Michigan Medicine, whose research focuses on the blood brain barrier. glioma tumors can cause abnormal blood vessels, interfering with normal blood flow.

The mice were injected with the nanoparticles. The brain tumor cells have a Peptide on the surface that is bound to aProtein. The integrity of the blood vessels was restored as the nanoparticles traveled through the bloodstream. The immune-suppressive myeloid cells were blocked from entering the tumor mass by the release of the nanoparticles. The immune cells were able to kill the tumor.

Nothing will get to your target if you don't have blood flow. That is the reason tumors are so smart. Castro said that the conduits are what allow the nanoparticles to reach the tumor.

The effect of radiation therapy on mice and patient cell lines was enhanced by the addition of the AMD3100 nanoparticle.

The researchers reintroduced the tumor in the mice whose tumors were eliminated. Half of the mice were cancer-free without any additional therapy. This suggests that the immune system was able to destroy the reintroduced cells because of the creation of immune memory. Castro said it boded well for at least delaying a repeat in people.

Every glioma recurs. It is important for glioma therapy to have this immunological memory.

After treatment, the mice had normal blood counts and no impact on their organs. The base of the nanoparticle has been tested in humans and shown to be safe. Before moving to a clinical trial, additional safety testing is necessary.

More information: Mahmoud S. Alghamri et al, Systemic Delivery of an Adjuvant CXCR4–CXCL12 Signaling Inhibitor Encapsulated in Synthetic Protein Nanoparticles for Glioma Immunotherapy, ACS Nano (2022). DOI: 10.1021/acsnano.1c07492 Journal information: ACS Nano Citation: A nanoparticle and inhibitor trigger the immune system, outsmarting brain cancer (2022, May 26) retrieved 26 May 2022 from https://phys.org/news/2022-05-nanoparticle-inhibitor-trigger-immune-outsmarting.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.