Revolutionary Hydrogel Combining Chemotherapy and Immunotherapy for Glioblastoma Treatment: Achieving 100% Survival Rate in Mice

2023-05-09 12:15:03

Researchers have developed a revolutionary hydrogel combining chemotherapy and immunotherapy to fight glioblastoma. Tested in mice, the postoperative gel has achieved a survival rate of 100%! It might represent the most promising therapeutic approach to date once morest this very aggressive form of cancer.

Glioblastoma, one of the most common forms of brain cancer, is classified by the WHO as a category 4 malignant astrocytic tumor due to its high aggressiveness. Characterized by cancerous cells very different from healthy cells and a rapid evolution, this cancer generally affects 2 to 3 people in 100,000. Life expectancy generally does not exceed 15 to 18 months following diagnosis, with a survival rate of around 5%.

In most cases, patients die before the tumor reaches a metastatic stage because it compresses the brain and increases intracranial pressure as it grows. Surgery is therefore the main medical recommendation when the tumor mass is accessible, also aiming to improve the chances of success of postoperative drug treatments.

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However, as Honggang Cui, a chemical and biomolecular engineer from Johns Hopkins University and co-designer of the new hydrogel, points out, “despite recent technological advances, there is an urgent need for new treatment strategies.” Indeed, glioblastomas have a strong tendency to recur following their ablation, because regarding 10% of residual tumor cells persist, impossible to remove completely by neurosurgery. Patients can thus experience relapses within 9 months of the operation, even while receiving postoperative chemotherapy or radiotherapy.

The new study, published in the journal PNAS, features a hydrogel designed to remove residual tumor cells and prevent patient recurrence. Composed of an anticancer drug and an antibody, the treatment combines two distinct therapeutic strategies: chemotherapy and immunotherapy. ” We don’t typically see 100% survival rates in mouse models of this disease. “says Betty Tyler, professor of neurosurgery at Johns Hopkins University and co-author of the study. This combination might significantly improve the survival rate of patients, with the hope of achieving a very low risk of recurrence following 5 years of remission following surgery, according to the expert.

An innovative hydrogel combining chemotherapy and immunotherapy

The hydrogel developed by Johns Hopkins University self-assembles into nanometric filaments when applied to the area of ​​tumor ablation (intracranially). This structure allows it to penetrate microgrooves inaccessible by surgery and injected drugs. The nanofilaments are composed of a water-soluble drug called paclitaxel (used in the chemotherapy of breast, lung and other cancers) and a molecular hydrogelator for the local delivery of aCD47 antibodies (a hydrophilic macromolecular antibody ). By uniformly filling the tumor resection cavity, the gel precisely releases the active molecules on a regular basis and for several weeks.

This combination of strategies, called “drug-delivered-by-drug”, is a real feat, because it is difficult to associate drugs with antibodies within the same excipient, due to their molecular divergences. Additionally, the hydrogel overcomes one of the greatest challenges in glioblastoma research, by sensitizing the tumor to block the signal antiphagocytaire (‘Don’t eat me’) mediated by aCD47.

Illustration of the effects of the hydrogel on the tumor cavity of glioblastoma. © Wang et al./PNAS

In glioblastoma, tumor cells become “smart” and express CD47 proteins, creating an immunosuppressive microenvironment that prevents them from being phagocytosed by macrophages (hence the term “don’t eat me”). This adaptation results in aggressive tumor growth, often allowing the tumor to reach a terminal stage in just a few months. aCD47 promote the creation of an immunostimulatory microenvironment and phagocytosis. In mice, the results were staggering with a 100% survival rate.

Activation of the “T memory” response

Additionally, the hydrogel was found to reactivate the anti-tumor T-cell response, normally deactivated by tumor-induced immunosuppression. Confirming this observation, the researchers reintroduced tumor cells into mice cured of glioblastoma. Result: the mice eliminated the tumor cells on their own, without the need for medication, thanks to a “memory T” response.

However, it is important to emphasize that the treatment is only effective in combination with surgery. Direct application of the gel without prior removal of the tumor would have resulted in only a 50% survival rate. According to the researchers, the surgery would allow the immune system to take time to relearn how to eliminate tumor cells.

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These results might also vary during the application in humans, not to mention the aCD47-related side effects
reported in previous research. Nevertheless, scientists believe that the hydrogel might potentially be used as an adjunct to other cancer treatments.

Hydrogel demonstration video:

Source : PNAS

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