Red Blood Cells Deliver Nanoparticles To Provoke Immune Response To Lung Metastases

Researchers at Harvard’s Wyss Institute have developed a way to deliver immune-stimulating agents to lung metastases. Their system involves nanoparticles loaded with an immune-stimulating agent that are attached to red blood cells. When injected into the blood stream, the red blood cells shed the nanoparticles as they squeeze through the narrow capillaries of the lungs, provoking immune cells to attack the tumors.

The EASI system delivers ImmunoBait particles into the cells that line the lungs’ blood vessels, where they release their chemokine payload. This action stimulates the body’s immune system to produce the chemokine on its own, and creates an immune response against lung metastases. Credit: Wyss Institute

Cancer frequently metastasizes to the lungs, where metastatic tumors release immunosuppressive agents to prevent immune system attack. This is the most common cause of metastasis-related death, but there is a lack of treatments for such metastases. These issues inspired researchers at the Wyss Institute to develop a new method that can provoke the immune system to attack such tumors.

“Our approach is the exact opposite of conventional cancer treatments that focus on getting the immune system to recognize and attack the primary tumor, because those tumors are often large and difficult for immune cells to penetrate,” said Zongmin Zhao, a researcher involved in the study. “We recognized that the high density of blood vessels in the lungs provides much better access to tumors there, offering a unique opportunity to induce an immune response by targeting the metastasis.”

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Their nanoparticles are loaded with CXCL10, a chemokine that can attract white blood cells. However, to selectively deliver the particles to the lungs, the researchers attached them to red blood cells which only release the particles when they squeeze through the narrow capillaries of the lungs. The nanoparticles are also covered in antibodies for a protein found in the blood vessel lining of the lungs, helping them to stick to the vessels and stay in place.

Scanning electron microscopy (SEM) image shows ImmunoBait nanoparticles, which are loaded with an immunostimulatory chemokine and attached to red blood cells. Credit: Wyss Institute

“Lung metastases deplete certain kinds of chemokines from their local environment, which means the signal that should attract beneficial white blood cells to fight the tumor is gone,” said Anvay Ukidve, another researcher involved in the study. “We hypothesized that providing that chemokine signal at the tumor site could help restore the body’s normal immune response and enable it to attack the tumors.”

So far, the researchers have tested their technology by injecting the nanoparticle-covered red blood cells into the blood stream of mice with lung metastases. They found that the treatment significantly increased the number and types of white blood cells within the lungs, decreased the number of lung metastases, and increased the survival of the mice.

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