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More Effective Mouse Brain Cancer Immunotherapy with Drug Coating

Nanoparticle coats can help immunotherapeutic agents cross the blood-brain barrier in mice and target brain tumors more effectively.


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May 26, 2022

Brain tumor cells

University of Michigan Logel Cancer Center

Coating an anticancer drug with nanoparticles can unleash an immune response that kills brain tumor cells, overcoming barriers that protect the brain from chemicals elsewhere in the body. In a small study using mice, encapsulated drugs used in combination with radiation therapy eliminated tumors in 67% of animals.

Glioblastoma is an aggressive type of tumor that forms when brain cells, called glial cells, grow out of control. This condition accounts for about one-third of brain tumor cases and has a very poor prognosis, with only 5% surviving 5 years after diagnosis.

These tumors are usually treated with surgery, followed by radiation therapy, and sometimes chemotherapy. However, while some drugs are expected to boost the body’s immune response to brain tumors, they often have difficulty crossing the blood-brain barrier to reach tumor cells.

“These drugs have so far been ineffective because they couldn’t cross the blood-brain barrier,” he said. Maria Castro At the University of Michigan School of Medicine.

Castro and her colleagues tested whether encapsulating the drug in synthetic nanoparticles made from proteins found naturally in the body helps reach the mouse brain. The team injected mice with either the drug alone or a nanoparticle-coated version. After 8 hours, the coated treated mice had 3 times more drug in the brain than the mice given the usual dose.

“This is an important discovery that enables the development and implementation of new treatment strategies for glioblastoma to enable effective delivery of the drug to the tumor,” says Castro.

Next, Castro’s team tested how well the drug works in mice with tumor cells transplanted into the brain, with or without nanoparticle coating. Mice treated with the encapsulated drug survived an average of 61 days after the tumor cells were first transplanted into the brain. Mice treated with the drug alone survived for 45 days. Studies of the brains of these mice have shown that the drug enhances the ability of immune cells to kill cancer.

In addition, the team found that the combination of nanoparticles-coated drugs and radiation therapy eliminated tumors in 67% of mice and allowed them to survive an average of 90 days from the moment the tumor cells were first transplanted. In contrast, all mice that received either radiation therapy or encapsulated drug alone died after about 60 days. Mice that received standard radiation therapy and did not receive the drug had the lowest survival rates, averaging 28 days.

“”[The nanoparticle-coated drug] It enhances the effectiveness of radiation therapy, the standard treatment for glioblastoma in human patients, “Castro said.

In a further experiment, the team transplanted another batch of tumor cells into the brain of mice previously receiving combination therapy. This reveals that these mice showed some immunity to new brain cancer cells, suggesting that treatment may act like a vaccine.

Treatment should be tested to see if it works in other animal models of glioblastoma before it is finally tested in humans.

“We expect this approach to be reflected in the clinic within the next few years,” says Castro.

Journal reference: ACS nanotechnology, DOI: 10.1021 / acsnano.1c07492

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More Effective Mouse Brain Cancer Immunotherapy with Drug Coating

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