Before mRNA vaccines became valuable preventive tools against COVID-19, scientists around the world were studying the potential use of technology in cancer therapies, but their success so far has been limited.
Now, scientists at China’s National Center for Nanoscience and Technology (NCNST) have designed a hydrogel to administer an mRNA vaccine with an immunity-boosting adjuvant. When melanoma was injected into mice, the vaccine remained active for at least 30 days, inhibiting tumor growth and preventing metastasis, according to results published in the Nano Letters magazine of the American Chemical Society.
The results showed that the hydrogel delivery system has the potential to help mRNA vaccines achieve long-lasting antitumor effects as cancer immunotherapy, the researchers said.
In COVID-19, mRNA vaccines contain the genetic information that tells 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 have to reach the lymph nodes for them to work. For its FDA-approved COVID-19 shot Comirnaty (BNT162b2), BioNTech used small fat particles known as lipid nanoparticles to protect basic mRNA information. The nanoparticles degrade and release the mRNA once they reach the target tissue. The same mRNA also degrades rapidly after protein translation.
This brief immune compromise works to prevent COVID-19, but in the treatment of cancer, a more lasting delivery of mRNA would be needed to achieve stable therapeutic results.
To this end, the NCNST team designed a hydrogel with graphene oxide and low weight polyethyleneimine. Graphene oxide can load pharmaceuticals efficiently thanks 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 the resiquimod agonist. Galderma TLR7 / 8 as 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 mRNA and adjuvant with the hydrogel and injected it under the skin of mice with melanoma tumors designed to express ovalbumin on its surface.
The hydrogel released the vaccine consistently, including both mRNA and adjuvant, into nanoparticles for at least 30 days, and migrated to the lymph nodes, the team demonstrated.
Animals that received only one injection of full therapy had significantly smaller tumors compared to mice that had free adjuvant and hydrogel-free mRNA, or those that received an unadjuvanted mRNA hydrogel. Mice that received full therapy also had the highest number of CD8 + T cells that entered tumors, the scientists found.
In addition, new mRNA gel treatment induced the highest level of ovalbumin-specific antibodies in the serum compared to others, suggesting that it not only inhibited tumor growth, but also prevented tumors from returning or they formed distant metastases. In fact, there were no observable metastases in the lung tissues of mice achieving full regimen, whereas the adjuvant-free mRNA-combined and non-adjuvant mRNA gel solution only partially relieved metastases compared to mice. control they obtained saline or just the ice administration system. , scientists reported.
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Biopharmaceutical companies that launched COVID-19 mRNA vaccines are still interested in applying the technology to cancer. But these are the first days and they have encountered many obstacles.
BioNTech and collaborator Roche reported an 8% response rate in 108 phase 1b patients who received a personalized mRNA cancer vaccine along with the Tecentriq checkpoint inhibitor. Moderna’s personalized cancer vaccine did not work alongside Merck’s Keytruda control point inhibitor in colorectal cancer in a small phase 1 study, although it reduced tumors in half of cancer patients. of head and neck.
The NCNST team suggests that its hydrogel system is potential as an efficient mRNA platform for use in cancer immunotherapy. “Collectively, the present study demonstrates the great potential of GLP-RO gel to achieve long-lasting and efficient immunotherapy against cancer,” the researchers wrote in the study.