An MRNA vaccine for cancer immunotherapy

Messenger RNA vaccines (mRNAs) to prevent COVID-19 have recently made headlines worldwide, but scientists have also been working on mRNA vaccines to treat or prevent other diseases, including some cancers. Now ACS researchers report ‘ Nano Letters developed a hydrogel that, when injected into mice with melanoma, slowly released RNA nanovaccines that shrank tumors and did not metastasize.

Cancer immunotherapy vaccines work similarly to mRNA vaccines for COVID-19, except that they activate the immune system to attack tumors instead of a virus. These vaccines contain mRNAs that encode proteins specifically produced by tumor cells. When the mRNA penetrates the antigen-presenting cells, they begin to make the tumor protein and display it on their surfaces, causing other immune cells to look for tumors that also make 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 it is usually cleared 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 a model antigen. The team mixed ovalbumin mRNA and an adjuvant with other compounds to form a hydrogel. The hydrogel slowly injected mRNA and adjuvant nanoparticles under the skin of mice over a period of 30 days with melanoma tumors designed to express ovalbumin. The mRNA vaccine activated T cells and stimulated antibody production, causing tumors in the treated mice to shrink. Unlike untreated mice, the vaccinated mice also showed no metastasis in the lung.

These results show that the hydrogel has great potential to achieve long-lasting and effective cancer immunotherapy with just a single treatment, the researchers say.