Flash nanoprecipitation assisted self-assembly of ionizable lipid nanoparticles for nucleic acid delivery

Misra, Bishal; Hughes, Krystal A.; Pentz, William H.; Samart, Parinya; Geldenhuys, Werner J.; Bobbala, Sharan

doi:10.1039/d4nr00278d

Cited by 2 publications

(1 citation statement)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Empty LNP without mRNA was prepared using the using the flash nanoprecipitation approach as described elsewhere. 43 The composition of empty LNP is similar to that of mRNA-1273 lipid nanoparticles. Empty LNP were 120 nm in size when analyzed using dynamic light scattering.…”

Section: Methodsmentioning

confidence: 90%

Intratumoral administration of mRNA-1273 vaccine delays melanoma growth in mice

Boehm,

Landreth,

Kilic

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Immunotherapies are advantageous for treating cancers; however, their efficacy is limited in unresponsive hosts with cold tumor microenvironments. This limitation primarily stems from the lack of infiltrating CD8+ T cells, which are major effectors of the anti-cancer immune response. Here, we demonstrate the effects of intratumoral (IT) injections of the COVID-19 mRNA vaccine on the impairment of tumor growth in mice. Methods: Established B16F10 subcutaneous tumor models in wild type mice were used to evaluate the tumor response from IT administration of mRNA-1273. We compared treatment outcomes, immune composition, and transcriptomic effects from mRNA-1273 using survival studies, intravital imaging, flow cytometry, single-cell RNA sequencing, and abscopal studies. The ability of mRNA-1273 to enhance immune checkpoint therapy response was also evaluated. Results: Tumor growth and survival studies following a single IT injection of the COVID-19 mRNA-1273 vaccine showed significant tumor suppression and prolonged survival in tumor-bearing mice. mRNA-1273 treatment resulted in a significant increase in CD8+ T cell infiltration into the tumor microenvironment, as observed using intravital imaging and flow cytometry. Further tumor growth suppression was achieved using additional mRNA-1273 treatments. Combination administration of mRNA-1273 with immune checkpoint therapies demonstrated enhanced effects, further delaying tumor growth and improving the survival time of tumor-bearing mice. Conclusion: IT injection of mRNA-1273 significantly reduced tumor growth and enhanced CD8+ T cells in the tumor microenvironment. Tumor suppression was further enhanced following multiple injections of mRNA-1273 or when combined with immune checkpoint therapies. This study demonstrates that mRNA vaccines may be used as adjuvants for immunotherapies.

show abstract

Section: Methodsmentioning

confidence: 90%