Like the hardiest weed, glioblastoma almost always springs back - usually within months after a patient’s initial brain tumor is surgically removed. That is why survival rates for this cancer are just 25% at one year and plummet to 5% by the five-year mark. One of the challenges of treating this disease is that surgeons can’t always remove every bit of tumor or glioma stem cells that might linger in the brain. Now, a powerful immunity-boosting postoperative treatment could transform the odds for patients with glioblastoma.

A key characteristic of glioblastoma is the aggressive nature of the tumor cells that infiltrate the surrounding tissues. As a result of this, surgeons are unable to clearly feel the boundaries between the tumor and normal tissue. The surgeons cannot remove as much as possible because all the tissues in the brain are vital. Hence, the tumor comes back again, sharply decreasing the survival rate after treatment. Now, scientists at the University of Wisconsin–Madison (Madison, WI, USA) have developed a hydrogel that can be injected into the brain cavity left behind by the excised tumor. The hydrogel delivery method works well because it completely fills the brain cavity, slowly releases the medicine into the surrounding tissue, and promotes the cancer-killing immune response.

The hydrogel is packed with nanoparticles designed to enter and reprogram certain types of immune cells called macrophages. These immune cells normally clean up infectious invaders in the body, but in the tumor environment, they can change into a form that instead suppresses the immune system and promotes cancer growth. And because of the inflammation created by surgery, these rogue macrophages flock to the surgical site, potentially fueling cancer relapse.

The nanoparticles can engineer the macrophages to target a glycoprotein called CD133, a marker for cancer stem cells. The researchers also added an antibody, CD47, that blocks a “don’t-eat-me” signal to promote macrophages to recognize the cancer cells. The preclinical results in mice models show that the hydrogel treatment successfully generated glioma stem cell-specific chimeric antigen receptor (CAR) macrophages - essentially engineering the immune cells on site to target and kill any lingering glioma stem cells.

If effective in humans, the hydrogel treatment could eliminate the need for postsurgical chemotherapy or radiation, reducing toxic side effects while also improving patient outcomes. The next step is testing the hydrogel in larger animal models and also monitoring long-term efficacy and toxicity beyond the four- to six-month period he previously studied. While the researchers initially focused on glioblastoma, the treatment approach could also be applied to other aggressive solid tumors, including breast cancer.

“It provides hope for preventing glioblastoma relapse,” said Quanyin Hu, an assistant professor in the University of Wisconsin–Madison School of Pharmacy’s Pharmaceutical Sciences Division. “We prove that it can actually eradicate these glioma stem cells, which can eventually prevent the glioblastoma from coming back. We can significantly improve survival.”

“We have a lot of work to do before it can be potentially translated into the clinic, but we feel confident that this is a very promising approach for bringing new hope to patients with glioblastoma so they can recover after surgery,” added Hu. “We hope we can do our work to be able to advance this technology to the clinic.” 

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