Lymph node-targeting lipid nanoparticle platform for mRNA vaccines

Delivering mRNA-encoded tumor antigens via a lipid nanoparticle optimized for lymph node targeting could help treat melanoma while minimizing off-target inflammation. Screening a library of reduction-responsive lipids with variations in head, tail and linker structures for their capacity to deliver a reporter RNA to mouse lymph nodes in vivo identified a lipid with a short tail, ester linker and methyl group in the amine head as a top candidate.

In a mouse model of melanoma expressing a model antigen, vaccination with an mRNA-encoded version of the antigen encapsulated in the lymph node-targeted lipid nanoparticle increased antigen-specific CD8⁺ T cell responses in the blood and tumor infiltration by macrophages and activated dendritic cells compared with delivery of the same antigen via the synthetic lipid used in the COVID-19 vaccine Comirnaty; treatment with both vaccines prevented tumor growth. Also in the model, treatment with an empty version of the lymph node-targeting vehicle induced less pro-inflammatory cytokine expression than treatment with the Comirnaty vehicle...