Cancer Therapy Using Lipid Nanoparticles to Encapsulate mRNA Mixtures Encoding Cytokines

Abstract

Compared with conventional cancer treatments such as chemotherapy and radiation therapy, mRNA gene therapy is a novel and promising approach. mRNA gene therapy has the advantage of being faster compared to other gene therapies and at a relatively low cost. Cytokines are potent modulators of the tumor microenvironment and were one of the first immunotherapies used to treat human cancers. The mRNA-generated cytokines have potential advantages over surface-engineered recombinant cytokines. Research has been showing effective therapeutic implications through local therapy by delivering immune-stimulated mRNAs to the tumor microenvironment (TME) with lipid nanoparticles (LNPs). Currently, new cytokine mRNA mixtures have been approved for their safe and efficient anticancer effects with low side effects, including a mixture of IL-12 and IL-27 mRNA, mRNA mixture encoding IL-23, IL-36, and OX40L, mRNA mixture encoding GM-CSF, IL15 sushi, IFNα, and scIL-12, etc. This review describes examples of enhancing efficacy through the use of LNPs to encapsulate mRNAs encoding cytokines and mRNA mixtures encoding two or more synergistic cytokines-lipid nanoparticles to improve therapeutic efficacy. Future research is required to consider translating in vitro and in vivo studies of mRNA mixture into clinical applications.