Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy

By M. Oberli, Andreas Reichmuth, J. R. Dorkin, Michael J. Mitchell, Owen S. Fenton, A. Jaklenec, Daniel G. Anderson, Robert Langer, D. Blankschtein. Nano letters (Print), 2016

632 citations recorded by the source corpus.

The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response. We show transfection of dendritic cells, macrophages, and neutrophils. The efficacy of the vaccine was tested in an aggressive B16F10 melanoma model. We found a strong CD 8 T cell activation after a single immunization. Treatment of B16F10 melanoma tumors with lipid nanoparticles containing mRNA coding for the tumor-associated antigens gp100 and TRP2 resulted in tumor shrinkage and extended the overall survival of the treated mice. The immune response can be further increased by the incorporation of the adjuvant LPS. In conclusion, the lipid nanoparticle formulation presented here is a promising vector for mRNA vaccine delivery, one that is capable of inducing a strong cytotoxic T cell response. Further optimization, including the incorporation of different adjuvants, will likely enhance the potency of the vaccine.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/bbef32a809af8b8964c65161aaa7334fc756d7d3

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Xuemei He
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Citations in the corpus

Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. (2019, neutral): “42,186”
Vaccine adjuvants: mechanisms and platforms (2023, background): “Oberli and his colleagues induced activation of CD8 T cells when using LNPs to deliver mRNA vaccines for the tumor-associated antigens gp100 and TRP2 to treat B16F10 melanoma, which led to tumor shrinkage and prolonged overall survival in mice.(266) In recent years, LNPs have been extensively tested”
Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines (2019, neutral): “18,19 20 – 22 Here, we describe rational evolution and selection of an improved formulation for IM administration of mRNA, focusing on the impact of the ionizable lipid component as the primary driver of expression and tolerability.”