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Glioblastoma: Immunotherapy-Loaded Gel Stops Cancer in Mice

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05/04/2023
medicalnewstoday.com

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Could a gel delivery method help improve the effectiveness of immunotherapy against brain cancer? Image credit: Bloomberg Creative/Getty Images.
  • Glioblastoma is a form of brain cancer that has very low survivability rates.
  • This is partly due to the fact that glioblastoma cancers evade detection by the immune system, and spread aggressively.
  • Many recent improvements in cancer survivability rates are due to the use of immunotherapies, but it is difficult for these to cross the blood-brain barrier to treat brain cancer.
  • Researchers have now created a gel that can be injected into the tumor cavity left following surgery. The gel, which contains immunotherapies to help the immune system to kill any remaining cancer cells, was tested in mice.

Though cancer death rates are improving overall, there are still some cancers that have poor survivability. One of those cancers is glioblastoma, a type of brain cancer that affects astrocyte cells in the brain.

Dr. Aung Bajaj, a medical oncologist and hematologist with Arizona Oncology, not involved in this study told Medical News Today that “glioblastoma multiforme is considered the most aggressive type of brain tumor, and patients who are diagnosed with glioblastoma multiforme typically live around 1-2 years.”

“It is treated with surgical resection followed by a combination of radiation and chemotherapy. If the cancer is maximally resected, the prognosis tends to be better. However, maximum resection is not always possible due to its infiltrative properties, where glioblastoma multiforme coexists with normal brain tissue, and extensive surgery for complete removal could compromise a patient’s neurologic function,” he noted.

Getting chemotherapies into the brain is challenging because of the blood-brain barrier, which prevents molecules over a certain size from reaching the brain.

One form of therapy given for glioblastoma is Gliadel wafers, which are small patches that slowly release a form of chemotherapy into the cavity left behind by the surgery, bypassing the problem posed by the blood-brain barrier.

Immunotherapies have greatly improved cancer survival rates for many other types of cancer, but the blood-brain barrier has made it challenging to replicate this success for brain cancer, explains Dr. Bajaj: “Blood-brain barrier limits the passage of therapeutic drugs crossing into the brain. Therefore, designing immunotherapy or anti-neoplastic molecules that effectively cross the blood-brain barrier has been difficult.”

In a recent study led by Dr. Honggang Cui, an associate professor from Johns Hopkins University, researchers showed that a type of gel they had developed containing immunotherapy agents improved survivability in mouse models.

The study findings appear in Proceedings of the National Academy of Sciences.

Researchers developed a hydrogel, a type of gel made mostly of water, to which they added paclitaxel, a chemotherapy drug that increases the number of a type of immune cell called macrophages, along with anti-CD47.

Anti-CD47 is an immunotherapy drug that blocks a receptor on the cancer cells which stops the cell from being destroyed by the immune system, thus encouraging the macrophages to destroy the cancer cells.

For the study, eight-to-ten-week-old mice that had glioblastoma introduced to their brains underwent resection surgery to remove the tumor. Another group of mice that had glioblastoma did not receive surgery.

The group of mice that received surgery, had a drug-containing hydrogel injected into the cavity left from surgery, and another group had a hydrogel that did not contain any drugs injected into the cavity. The mice that did not have surgery to remove the tumor had the gel directly injected into the site of the glioblastoma.

Using a gel rather than a different delivery system, such as just injecting the drugs in water, was important to keep the drugs at the site, explained Dr. Cui to Medical News Today:

“With gel when they go from the solution to a gel it has very good local retention it will stay where they put it […] So the therapeutic gel will allow them to stay where they are put and also importantly, they stay here they can gradually and slowly release delivering compounds.”

Researchers showed that the gel formed in the tumor cavity that remained after 10 minutes, and was found to gradually biodegrade over 45 days.

They found that the size of the tumor that remained in the brain was significantly reduced in the mice that received the immunotherapy-containing gel compared to the control gel.

Not only did researchers observe that the tumor was significantly reduced, but they also showed that the mice which had resection surgery and received the immunotherapy containing hydrogel had a 100% survival rate.

This compared to just 25% of the mice that did not receive the immunotherapy. Surgery was found to be essential as applying the gel directly in the brain without surgical removal of the tumor resulted in a 50% survival rate.

This proof of concept paper showed that the use of the hydrogen in the tumor cavity led to the creation of an “immune-stimulating tumor microenvironment and triggers an anti-tumor T cell response,” explained Dr. Manmeet S. Ahluwalia, chief of medical oncology, chief Scientific officer and deputy director at Miami Cancer Institute, who was not involved in the research.

He told MNT that: “In summary, this treatment approach may help to improve outcomes for patients with recurrent glioblastoma. This breakthrough new approach of hydrogel-based therapy, while a long way from clinical practice, carries a significant potential to improve treatment outcomes and patient survival.”

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Schedule6 Jun 2023