Differentiation of human embryonic stem cells into immunostimulatory dendritic cells under feeder-free culture conditions.

Authors

Zhen Su
Carole Frye
Kyung-Mi Bae
Vicky Kelley
Johannes Vieweg, Nova Southeastern UniversityFollow

Publication Title

Clinical cancer research : an official journal of the American Association for Cancer Research

Publisher

American Association for Cancer Research

ISSN

1078-0432

Publication Date

10-1-2008

Keywords

Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, Cell Culture Techniques, Cell Differentiation, Dendritic Cells, Embryonic Stem Cells, Flow Cytometry, Forkhead Transcription Factors, Histocompatibility Antigens Class II, Humans, Immunotherapy, Interleukin-12, Peptides, RNA, Messenger, Th1 Cells

Abstract

PURPOSE: The objective of this study was to develop a scalable and broadly applicable active immunotherapy approach against cancer, circumventing the limitations typically encountered with autologous vaccination strategies. We hypothesized that human embryonic stem cells (hESC) can serve as a virtually unlimited source for generating dendritic cells (DC) with potent antigen-presenting function. Here, we investigated the developmental processes and requirements for generating large numbers of mature, antigen-presenting DC from pluripotent hESC.

EXPERIMENTAL DESIGN: A feeder cell-free culture system was developed to differentiate hESC into mature DC sequentially through hematopoietic and myeloid precursor stages.

RESULTS: Using this method, we were able to yield large numbers of mature immunostimulatory DC from hESC to enable clinical investigation. Upon activation, the hESC-derived DC secreted interleukin-12p70, migrated in response to MIP-3beta, and exhibited allostimulatory capacity. Most importantly, antigen-loaded, hESC-derived DC were capable of stimulating potent antigen-specific CD8(+) T-cell responses in an HLA class I-matched semiallogeneic assay system. Moreover, HLA class II-mismatched hESC-derived DC induced a potent Th1-type cytokine response without expanding FOXP3(+) regulatory T cells in vitro.

CONCLUSIONS: These data suggest the development of a novel active immunotherapy platform to stimulate potent T-cell immunity in patients with intractable diseases, such as cancer or viral infection.

DOI

10.1158/1078-0432.CCR-08-0309

Volume

14

Issue

19

First Page

6207

Last Page

6217

Disciplines

Medicine and Health Sciences

NSUWorks Citation

Su, Zhen; Frye, Carole; Bae, Kyung-Mi; Kelley, Vicky; and Vieweg, Johannes, "Differentiation of human embryonic stem cells into immunostimulatory dendritic cells under feeder-free culture conditions." (2008). NSU-MD Faculty Articles. 47.
https://nsuworks.nova.edu/hpd_md_facarticles/47