New hydrogel shrinks tumors in melanoma mice model

Recently, messenger RNA, also called mRNA, vaccines, to combat the COVID-19 infection have made headlines worldwide, but researchers have already been experimenting with mRNA vaccines to prevent or cure other illnesses, including certain types of cancer.

Vaccine

Vaccine. Image Credit: New Africa/Shutterstock.com

Researchers have now reported in ACS’ Nano Letters jocular that they have created a hydrogel that, when administered into mice with melanoma, gradually discharged RNA nanovaccines that reduced the size of tumors and prevented them from metastasizing.

Cancer immunotherapy vaccines function in almost the same way as the mRNA vaccines to prevent the COVID-19 disease, except that they trigger the immune system to fight tumors rather than a virus. Such vaccines contain mRNA that encodes proteins specifically produced by cancer cells. As mRNAs penetrate the antigen-presenting cells, they begin to produce the tumor protein and display it on their surfaces, stimulating other immune cells to search and kill the tumors that produce this protein as well.

But mRNA is not a stable compound and is quickly decomposed by the body enzymes. For cancer immunotherapy, the team has attempted to use nanoparticles to protect and transport mRNA, but these particles are normally eliminated from the body in less than 1 or 2 days post-injection. Guangjun Nie, Hai Wang, and collaborators wanted to create a hydrogel that would gradually discharge mRNA nanoparticles when administered under the skin, together with an adjuvant—a molecule that helps trigger the immune system.

The researchers developed their system by using ovalbumin—a protein present in chicken egg whites—as a model antigen. Next, they combined an adjuvant and ovalbumin mRNA with other compounds to create a hydrogel.

When the hydrogel was injected under the skin of mice with melanoma tumors designed to express ovalbumin, it gradually released adjuvant nanoparticles and mRNA over a period of 30 days. The mRNA vaccine triggered T cells and stimulated the production of antibodies, which shrank the tumors in the treated mice. Moreover, unlike the untreated mice, no lung metastases were detected on the vaccinated mice.

These findings indicate that the hydrogel has excellent potential to achieve efficient and long-lasting cancer immunotherapy using just one treatment, concluded the researchers.

Source:
Journal reference:

Yin, Y., et al. (2021) In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy. Nano Letters. doi.org/10.1021/acs.nanolett.0c05039.

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