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Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response.
- Source :
-
Nature communications [Nat Commun] 2020 Feb 28; Vol. 11 (1), pp. 1110. Date of Electronic Publication: 2020 Feb 28. - Publication Year :
- 2020
-
Abstract
- Targeted delivery of a nanovaccine loaded with a tumor antigen and adjuvant to the lymph nodes (LNs) is an attractive approach for improving cancer immunotherapy outcomes. However, the application of this technique is restricted by the paucity of suitable tumor-associated antigens (TAAs) and the sophisticated technology required to identify tumor neoantigens. Here, we demonstrate that a self-assembling melittin-lipid nanoparticle (α-melittin-NP) that is not loaded with extra tumor antigens promotes whole tumor antigen release in situ and results in the activation of antigen-presenting cells (APCs) in LNs. Compared with free melittin, α-melittin-NPs markedly enhance LN accumulation and activation of APCs, leading to a 3.6-fold increase in antigen-specific CD8 <superscript>+</superscript> T cell responses. Furthermore, in a bilateral flank B16F10 tumor model, primary and distant tumor growth are significantly inhibited by α-melittin-NPs, with an inhibition rate of 95% and 92%, respectively. Thus, α-melittin-NPs induce a systemic anti-tumor response serving as an effective LN-targeted whole-cell nanovaccine.
- Subjects :
- Animals
Antigen-Presenting Cells immunology
Antigens, Neoplasm immunology
Cancer Vaccines administration & dosage
Cancer Vaccines chemistry
Cancer Vaccines metabolism
Cell Line, Tumor
Cytokines immunology
Female
Immunotherapy
Lipids administration & dosage
Lipids chemistry
Lymph Nodes metabolism
Melitten chemistry
Melitten immunology
Melitten metabolism
Mice
Mice, Inbred C57BL
Nanoparticles chemistry
Nanoparticles metabolism
Neoplasms therapy
T-Lymphocytes immunology
Xenograft Model Antitumor Assays
Cancer Vaccines immunology
Drug Delivery Systems
Lymph Nodes immunology
Melitten administration & dosage
Nanoparticles administration & dosage
Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32111828
- Full Text :
- https://doi.org/10.1038/s41467-020-14906-9