Before mRNA vaccines became valuable preventive tools against COVID-19, scientists around the world were studying the potential use of technology in cancer therapy, but their success has so far been limited.
Now, scientists at China’s National Center for Nanoscience and Technology (NCNST) have designed a hydrogel to release an mRNA vaccine with an immune-boosting adjuvant. When injected into mice with melanoma, the vaccine remained active for at least 30 days, inhibiting tumor growth and preventing metastases, according to results published in the American Chemical Society’s Nano Letters magazine.
The results showed that the hydrogel delivery system has the potential to help mRNA vaccines achieve long-lasting anti-tumor effects as cancer immunotherapy, the researchers said.
In COVID-19, mRNA vaccines carry genetic information that instructs the body to produce a specific viral protein to trigger the desired immune response. In cancer, vaccines are usually designed to translate tumor-associated antigens so that the immune system can recognize and eliminate the cancer.
The problem is that RNA is very unstable, and mRNA vaccines need to reach the lymph nodes to function. For Comirnaty (BNT162b2) FDA-approved COVID-19 shot, BioNTech used small fat particles known as lipid nanoparticles to protect basic information about mRNA. The nanoparticles degrade and release mRNA once they reach the target tissue. Also, mRNA degrades rapidly after translation of proteins.
That short immune commitment works to prevent COVID-19, but in the treatment of cancer, a more sustainable delivery of mRNA would be needed to achieve stable therapeutic results.
To this end, the NCNST team designed a hydrogel with graphene oxide and lightweight polyethyleneimine. Graphene oxide can efficiently load drugs due to its large surface area, and polyethyleneimine binds the mRNA content for translation. To further enhance the stimulation and expansion of antigen-specific CD8 + T cells – which are critical for antitumor immune responses – in the presence of a hostile tumor microenvironment, the team added Galderma’s TLR7 / 8 agonist resiquimod as an adjuvant.
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To test their mRNA platform, the researchers used ovalbumin, a protein found in chicken egg whites, as a model antigen. They mixed ovalbumin and adjuvant mRNA with hydrogel and injected it under the skin of mice with melanoma tumors designed to express ovalbumin on their surface.
The hydrogel consistently released the vaccine – including both mRNA and adjuvant – into nanoparticles for at least 30 days and migrated to the lymph nodes, the team said.
Animals that received a single injection of full therapy had significantly smaller tumors compared to mice that received free adjuvant and hydrogel-free mRNA or those that received a nonadjuvanted mRNA hydrogel. Mice that received full therapy also had the highest number of CD8 + T cells that entered the tumors, the scientists found.
Moreover, the new mRNA gel treatment induced the highest level of serum ovalbumin-specific antibodies compared to others, suggesting that it not only inhibited tumor growth, but also prevented tumor return or distant metastasis. Indeed, there were no observable metastases in the lung tissues of mice that achieved full regimen, while the free combination of adjuvant mRNA and nonadjuvanted mRNA gel solution only partially ameliorated metastases compared to control mice that received saline. or just the gel release system, the scientists reported.
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Biopharmaceutical companies that have introduced COVID-19 mRNA vaccines are still interested in applying cancer technology. But these are the first days and they have encountered many obstacles.
BioNTech and co-worker Roche reported a response rate of only 8% in 108 phase 1b patients in the study who received a personalized mRNA cancer vaccine along with the Tecentriq checkpoint inhibitor. The Moderna personalized cancer vaccine failed to work with Merck Keytruda’s colorectal cancer control inhibitor in a small phase 1 study, although it reduced tumors in half of head and neck cancer patients.
The NCNST team suggests that its hydrogel system has the potential as an effective mRNA platform for use in cancer immunotherapy. Collectively, this study demonstrates the great potential of GLP-RO gel in achieving sustainable and effective immunotherapy against cancer, the researchers wrote in the study.