New injectable gel holds promise for tough-to-treat brain tumours

Glioblastoma almost always returns, usually months after the patient’s initial brain tumour is surgically removed. It is like the toughest weed. As a result, just 25% of people with this malignancy survive one year after diagnosis, and only 5% do so after five years.

One of the challenges in treating this sickness is that surgeons can’t always completely remove all of the tumour or glioma stem cells that may still be in the brain.

“In glioblastoma, the aggressiveness of the tumour cells causes them to invade the tissues around. As a result, it is difficult for the surgeon to distinguish between the tumour and normal tissue, and because all of the brain’s tissues are crucial, it is impossible to remove as much as possible,” according to Quanyin Hu, an assistant professor in the Pharmaceutical Sciences Division of the University of Wisconsin-Madison School of Pharmacy. Because of this, the likelihood that the tumour will return after treatment is complete dramatically decreases.

As a result, there is a significantly reduced chance that the tumour will come back when therapy is finished.

A strong postoperative immune booster, however, developed by Hu’s Cell-Inspired Personalized Therapeutic (CIPT) Lab may improve the prognosis for glioblastoma patients. Regarding the use of the treatment in mice models of human glioblastoma, Hu and his coworkers published their findings in the journal Science Translational Medicine this month.

According to Hu, “it offers hope for avoiding glioblastoma relapse.” “We demonstrate that it is capable of eliminating these glioma stem cells, ultimately preventing the recurrence of the glioblastoma. We can greatly increase survival.

A hydrogel that can be injected into the brain cavity left behind by the removed tumour was created by Hu’s lab. According to Hu, the hydrogel delivery method is effective because it completely fills the brain cavity, gradually releases the medication into the surrounding tissue, and stimulates the immune system’s ability to fight cancer.

The hydrogel is loaded with nanoparticles made to enter and rewire specific immune cell types known as macrophages. In the tumour environment, these immune cells can transform into a form that instead suppresses the immune system and aids in the development of cancer. Normally, these immune cells clear the body of infectious invaders. These rogue macrophages also congregate at the surgical site as a result of the inflammation caused by surgery, which may encourage cancer relapse.

“We want to take advantage of these macrophages and turn them from enemy to ally,” Hu said.

To do this, the nanoparticles can instruct the macrophages to target the glycoprotein cancer stem cell marker CD133. In order to aid macrophages in detecting the cancer cells, Hu’s team also added an antibody called CD47 that suppresses a “don’t eat me” signal. Preclinical studies in mice models showed that the hydrogel treatment successfully generated chimeric antigen receptor (CAR) macrophages that were selective for glioma stem cells. This successfully altered the neighbourhood immune system to locate and get rid of any leftover glioma stem cells.

If successful in people, the hydrogel treatment could do away with the need for postoperative radiation or chemotherapy, minimising harmful side effects while also improving patient outcomes.

The hydrogel will be tested in larger animal models in Hu’s upcoming research, and he will also keep an eye on its long-term efficacy and toxicity beyond the four to six months he previously examined.

Hu says, “We feel confident that this is a very promising approach for bringing new hope to patients with glioblastoma so they can recover after surgery.”

However, there is still much work to be done before it could possibly be translated into the clinic. “We hope we can complete our tasks so that this technology can be advanced to the clinic.”

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Although Hu’s team is initially concentrating on glioblastoma, he points out that the therapeutic strategy could also be used to treat other aggressive solid tumours, such as breast cancer. “Our strategy is to locally engineer these macrophages and to take advantage of the macrophages in the postsurgical areas,” he claims. “We are confident that the majority of solid tumours with high invasive characteristics will fall under this scenario.”

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