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Immunology. 2017 Nov;152(3):462-471. doi: 10.1111/imm.12783. Epub 2017 Jul 27.

Artificial human antigen-presenting cells are superior to dendritic cells at inducing cytotoxic T-cell responses.

Author information

1
Department of Basic Medicine, Huzhou University School of Medicine, Huzhou, Zhejiang, China.
2
Department of General Surgery, Sir Runrun Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
3
Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
4
Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, Yale Cancer Center, New Haven, CT, USA.
5
Department of Clinical Medicine, Huzhou University School of Medicine, Huzhou, Zhejiang, China.
6
StemImmune Inc., San Diego, CA, USA.
7
Institute for Cancer Biology and Stem Cell Research, Huzhou University, Huzhou, Zhejiang, China.

Abstract

Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T-cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen-specific CTLs were then induced using either peptide-loaded mature DCs (mDCs) or aAPCs, and their activities were analysed using both ELISpot and cytotoxicity assays. We found that the aAPCs induced significantly stronger tumour antigen-specific CTL responses than the controls, which included both mDCs and aAPCs loaded with empty nanoparticles. Moreover, frozen CTLs that were generated by exposure to aAPCs retained the capability to eradicate HLA-A2-positive tumour antigen-bearing cancer cells. These results indicated that aAPCs are superior to DCs when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPCs with PLGA-NPs encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials.

KEYWORDS:

artificial antigen-presenting cells; cytotoxic T lymphocytes; dendritic cells; peptide; poly(lactide-co-glycolide) acid

PMID:
28664991
PMCID:
PMC5629434
DOI:
10.1111/imm.12783
[Indexed for MEDLINE]
Free PMC Article

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