The immunogenicity of virus-derived 2A sequences in immunocompetent individuals.

Details

Serval ID
serval:BIB_025BD6B93D5E
Type
Article: article from journal or magazin.
Collection
Publications
Title
The immunogenicity of virus-derived 2A sequences in immunocompetent individuals.
Journal
Gene therapy
Author(s)
Arber C., Abhyankar H., Heslop H.E., Brenner M.K., Liu H., Dotti G., Savoldo B.
ISSN
1476-5462 (Electronic)
ISSN-L
0969-7128
Publication state
Published
Issued date
09/2013
Peer-reviewed
Oui
Volume
20
Number
9
Pages
958-962
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Genetic engineering of T cells for adoptive immunotherapy in cancer patients has shown significant promise. To ensure optimal antitumor activity and safety, the simultaneous expression of multiple genes is frequently required, and short viral-derived 2A sequences are increasingly preferred for this purpose. Concerns exist, however, that these virus-derived sequences may induce unwanted immune responses, and thus diminish persistence of the gene-modified cells after adoptive transfer. Whereas such responses were absent in immunocompromised recipients, potential immunogenicity in immunocompetent individuals remains a concern. We now address whether ex vivo T cell responses can be elicited against the most widely used 2A sequences (2A-Thosea asigna virus (TAV) or 2A-equine rhinitis virus (ERAV), specifically) in immunocompetent individuals. We used a potent ex vivo culture system previously validated to induce T cell responses even against weakly immunogenic antigens. Of the sixteen donors tested, only five released very low levels of interferon-γ in response to 2A-TAV peptide mixtures (single peptide specificity in three donors, adjacent self-antigen peptide specificity in one donor and nonspecific reactivity in one donor). None of them produced cytotoxic activity or responded to 2A-ERAV. These results suggest that exposure to viral-derived 2A sequences is unlikely to produce unwanted T cell responses in immunocompetent individuals and further supports their continued use for studies of human gene therapy.
Keywords
Amino Acid Sequence, Antigens/immunology, Aphthovirus/genetics, Aphthovirus/immunology, Cell Line, Genetic Vectors, Healthy Volunteers, Humans, Immunocompetence, Immunotherapy, Adoptive, Interferon-gamma/biosynthesis, Interferon-gamma/immunology, Lymphocyte Activation, Molecular Sequence Data, Peptides/chemistry, Peptides/immunology, RNA Viruses/genetics, RNA Viruses/immunology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism
Pubmed
Web of science
Create date
01/11/2019 9:58
Last modification date
02/11/2019 6:26
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