Dataset Information

Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response.

ABSTRACT: Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems. Here we show that ?-Al(2)O(3) nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that ?-Al(2)O(3) nanoparticles delivered antigens to autophagosomes in dendritic cells, which then presented the antigens to T cells through autophagy. Immunization of mice with ?-Al(2)O(3) nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. These results suggest that ?-Al(2)O(3) nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines.

SUBMITTER: Li H

PROVIDER: S-EPMC3483867 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response.

Li Haiyan H Li Yuhuan Y Jiao Jun J Hu Hong-Ming HM

Nature nanotechnology 20110918 10

Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems. Here we show that α-Al(2)O(3) nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that α-Al(2)O(3 ...[more]

PMID: 21926980

Similar Datasets

Project description:BackgroundAutophagy as a cellular pathway facilitates several immune responses against infection. It also eliminates invading pathogens through transferring content between the cytosol and the lysosomal vesicles and contributes to the cross-presentation of exogenous antigens to T lymphocytes via MHC class I pathway. Autophagy induction is one of the main targets for new drugs and future vaccine formulations. Nanoparticles are one of the candidates for autophagy induction. Cysteine Peptidase A (CPA) and Cysteine Peptidase B (CPB) are two members of papain family (Clan CA, family C1) enzyme that have been considered as a virulence factor of Leishmania (L.) major, making them suitable vaccine candidates. In this research, Leishmania major cysteine peptidase A and B (CPA and CPB) conjugation to alpha alumina nanoparticle was the main focus and their entrance efficacy to macrophages was assessed.MethodsFor this purpose, CPA and CPB genes were cloned in expression vectors. Related proteins were extracted from transformed Escherichia coli (E. coli) and purified using Ni affinity column. Alpha alumina nanoparticles were conjugated to CPA/CPB proteins using Aldehyde/Hydrazine Reaction. Autophagy induction in macrophages was assessed using acridine orange staining.ResultsCPA/CPB protein loading to nanoparticles was confirmed by Fourier Transform Infrared Spectroscopy. α-alumina conjugated CPA/CPB antigen uptake by macrophages at different concentrations was confirmed using fluorescence microscope and flowcytometry. Highly efficient CPA/CPB protein loading to α-alumina nanoparticles and rapid internalization to macrophages introduced these nanocarriers as a delivery tool. Acridine orange staining demonstrated higher autophagy induction in CPA/CPB protein conjugated with α-alumina nanoparticles.Conclusionα-alumina nanoparticles may be a promising adjuvant in the development of therapeutic leishmania vaccines through antigen delivery to intracellular compartments, induction of autophagy and cross presentation to CD8 lymphocytes.

Dataset Information

Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response.

Publications

Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets