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In vivo Targeting of DNA Vaccines to Dendritic Cells via the Mannose Receptor Induces Long‐Lasting Immunity against Melanoma
Author(s) -
Moku Gopikrishna,
Vangala Swathi,
Gulla Suresh Kumar,
Yakati Venu
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000364
Subject(s) - mannose receptor , in vivo , mannose , cd11c , dendritic cell , immunology , melanoma , immune system , cancer research , chemistry , microbiology and biotechnology , biology , in vitro , biochemistry , macrophage , gene , phenotype
Herein, we report effective, C‐type lectin mannose receptor (MR)‐selective, in vivo dendritic cell (DC)‐targeting lipid nanoparticles (LNPs) of a novel lipid‐containing mannose‐mimicking di‐shikimoyl‐ and guanidine head group and two n ‐hexadecyl hydrophobic tails (DSG). Subcutaneous administration of LNPs of the DSG/p‐CMV‐GFP complex showed a significant expression of green fluorescence protein in the CD11c + DCs of the neighboring lymph nodes compared to the control LNPs of the BBG/p‐CMV‐GFP complex. Mannose receptor‐facilitated in vivo DC‐targeted vaccination (s.c.) with the electrostatic complex of LNPs of DSG/pCMV‐MART1 stimulated long‐lasting (270 days post B16F10 tumor challenge) antimelanoma immunity under prophylactic conditions. Remarkably, under therapeutic settings, vaccination (s.c.) with LNPs of the DSG/pCMV‐MART1 complex significantly delayed melanoma growth and improved the survival of mice with melanoma. These findings demonstrate that this nonviral delivery system offers a resilient and potential approach to deliver DNA vaccines encoding tumor antigens to DCs in vivo with high efficacy.