MRNA vaccine for cancer immunotherapy

Messenger RNA (mRNA) vaccines to prevent COVID-19 have recently appeared around the world, but scientists are also working on mRNA vaccines to treat or prevent other diseases, including some forms of cancer. Now researchers are reporting to ACS Nano words they developed a hydrogel that, when injected into melanoma mice, slowly released RNA nanovaccines that shrunk tumors and prevented them from metastasizing.

Cancer immunotherapy vaccines work similarly to mRNA vaccines against COVID-19, except that they activate the immune system to attack tumors instead of viruses. These vaccines contain mRNA that encodes proteins specifically made from tumor cells. When mRNA enters the cells that present the antigen, they begin to produce a tumor protein and display it on their surfaces, triggering other immune cells to search for and destroy tumors that also produce this protein. However, mRNA is an unstable molecule that is rapidly broken down by enzymes in the body. For cancer immunotherapy, researchers have tried to use nanoparticles to protect and deliver mRNA, but they are usually removed from the body within 1-2 days after injection. Guangjun Nie, Hai Wang and colleagues wanted to develop a hydrogel that, when injected under the skin, would slowly release mRNA nanoparticles, along with an adjuvant – a molecule that helps activate the immune system.

To develop their system, the researchers used ovalbumin (a protein found in chicken egg whites) as an antigen model. The team mixed ovalbumin mRNA and adjuvant with other compounds to form a hydrogel. When mice were injected subcutaneously with melanoma tumors designed to express ovalbumin, the hydrogel slowly released mRNA and adjuvant nanoparticles over 30 days. The mRNA vaccine activated T cells and stimulated antibody production, causing tumor shrinkage in treated mice. Also, unlike untreated mice, vaccinated mice did not show lung metastases. These results show that the hydrogel has great potential for achieving long-term and effective cancer immunotherapy with just one treatment, the researchers say.

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The authors acknowledge funding from the National Key Research and Development Program of China, the National Science Foundation of China, the Chinese Academy of Sciences, and the KC Wong Education Foundation.

A summary of the paper will be available Feb. 17 at 8 a.m. Eastern Time here: http: // pubs.acsorg /doi /abs /10.1021 /acsnanolett.0c05039

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