Optimum in vitro expansion of human antigen-specific CD8 T cells for adoptive transfer therapy.

Details

Serval ID
serval:BIB_1AC9A366B9C2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Optimum in vitro expansion of human antigen-specific CD8 T cells for adoptive transfer therapy.
Journal
Clinical and experimental immunology
Author(s)
Montes M., Rufer N., Appay V., Reynard S., Pittet M.J., Speiser D.E., Guillaume P., Cerottini J.C., Romero P., Leyvraz S.
ISSN
0009-9104
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
142
Number
2
Pages
292-302
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Increasing evidence suggests that adoptive transfer of antigen-specific CD8(+) T cells could represent an effective strategy in the fight against chronic viral infections and malignancies such as melanoma. None the less, a major limitation in the implementation of such therapy resides in the difficulties associated with achieving rapid and efficient expansion of functional T cells in culture necessary to obtain the large numbers required for intravenous infusion. Recently, the critical role of the cytokines interleukin (IL)-2, IL-7 and IL-15 in driving T cell proliferation has been emphasized, thus suggesting their use in the optimization of expansion protocols. We have used major histocompatibility complex (MHC) class I/peptide multimers to monitor the expansion of antigen-specific CD8 T lymphocytes from whole blood, exploring the effect of antigenic peptide dose, IL-2, IL-7 and IL-15 concentrations on the magnitude and functional characteristics of the antigen-specific CD8(+) T cells generated. We show here that significant expansions of antigen-specific T cells, up to 50% of the CD8(+) T cell population, can be obtained after a single round of antigen/cytokine (IL-2 or IL-15) stimulation, and that these cells display good cytolytic and interferon (IFN)-gamma secretion capabilities. Our results provide an important basis for the rapid in vitro expansion of autologous T cells from the circulating lymphocyte pool using a simple procedure, which is necessary for the development of adoptive transfer therapies.
Keywords
Adoptive Transfer, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cell Culture Techniques, Cell Division, Cell Line, Dose-Response Relationship, Immunologic, Epitopes, T-Lymphocyte, Humans, Immunophenotyping, Interleukin-15, Interleukin-2, Interleukin-7, Melanoma, Neoplasm Proteins
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:13
Last modification date
20/08/2019 12:51
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