Recently, the use of mRNA-based vaccines for cancer immunotherapy has gained growing attention. Several studies have shown that mRNA delivered in a vectorized format can generate a robust and efficient immune response. In this work, a new lipopolyplex vector (multi-LP), incorporating the immune adjuvant α-galactosylceramide (α-GalCer) and a multivalent cationic lipid, was proposed for the in vivo delivery of mRNA into antigen-presenting cells. We demonstrate that dendritic cells (DCs) can be targeted in vivo by intravenous administration of a α-GalCer-/mRNA-loaded multi-LP vector, without the need for its functionalization with cell-specific antibodies or ligands. The multi-LP nanoparticles loaded with a reporter mRNA efficiently led to high expression of the enhanced green fluorescence protein in DCs both in vitro and in vivo, exhibiting an intrinsic selectivity for DCs. Finally, the TRP2-mRNA/α-GalCer-based multi-LP vaccine induced a significant therapeutic effect against a highly malignant B16-F10 melanoma tumor. This study provides the first evidence that a combination of antigen-mRNA and α-GalCer can be used as an effective antitumor vaccine, inducing strong innate and adaptive immune responses.

Codelivery of mRNA with α-galactosylceramide using a new lipopolyplex formulation induces a strong antitumor response upon intravenous administration / M.L. Guevara, Z. Jilesen, D. Stojdl, S. Persano. - In: ACS OMEGA. - ISSN 2470-1343. - 4:8(2019), pp. 13015-13026. [10.1021/acsomega.9b00489]

Codelivery of mRNA with α-galactosylceramide using a new lipopolyplex formulation induces a strong antitumor response upon intravenous administration

S. Persano
Ultimo
2019

Abstract

Recently, the use of mRNA-based vaccines for cancer immunotherapy has gained growing attention. Several studies have shown that mRNA delivered in a vectorized format can generate a robust and efficient immune response. In this work, a new lipopolyplex vector (multi-LP), incorporating the immune adjuvant α-galactosylceramide (α-GalCer) and a multivalent cationic lipid, was proposed for the in vivo delivery of mRNA into antigen-presenting cells. We demonstrate that dendritic cells (DCs) can be targeted in vivo by intravenous administration of a α-GalCer-/mRNA-loaded multi-LP vector, without the need for its functionalization with cell-specific antibodies or ligands. The multi-LP nanoparticles loaded with a reporter mRNA efficiently led to high expression of the enhanced green fluorescence protein in DCs both in vitro and in vivo, exhibiting an intrinsic selectivity for DCs. Finally, the TRP2-mRNA/α-GalCer-based multi-LP vaccine induced a significant therapeutic effect against a highly malignant B16-F10 melanoma tumor. This study provides the first evidence that a combination of antigen-mRNA and α-GalCer can be used as an effective antitumor vaccine, inducing strong innate and adaptive immune responses.
Settore BIO/13 - Biologia Applicata
2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/958882
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