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Molecular Therapy
Article . 2015 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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Molecular Therapy
Article
License: CC BY NC ND
Data sources: UnpayWall
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Molecular Therapy
Article . 2015
License: CC BY NC ND
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Engager T Cells: A New Class of Antigen-specific T Cells That Redirect Bystander T Cells

Authors: Iwahori, Kota; Kakarla, Sunitha; Velasquez, Mireya P; Yu, Feng; Yi, Zongzhen; Gerken, Claudia; Song, Xiao-Tong; +1 Authors

Engager T Cells: A New Class of Antigen-specific T Cells That Redirect Bystander T Cells

Abstract

Adoptive immunotherapy with antigen-specific T cells has shown promise for the treatment of malignancies. However, infused T cells are unable to redirect resident T cells, limiting potential benefit. While the infusion of bispecific T-cell engagers can redirect resident T cells to tumors, these molecules have a short half-life, and do not self amplify. To overcome these limitations, we generated T cells expressing a secretable T-cell engager specific for CD3 and EphA2, an antigen expressed on a broad range of human tumors (EphA2-ENG T cells). EphA2-ENG T cells were activated and recognized tumor cells in an antigen-dependent manner, redirected bystander T cells to tumor cells, and had potent antitumor activity in glioma and lung cancer severe combined immunodeficiency (SCID) xenograft models associated with a significant survival benefit. This new class of tumor-specific T cells, with the unique ability to redirect bystander T cells, may be a promising alternative to current immunotherapies for cancer.

Keywords

Male, Lung Neoplasms, CD3 Complex, T-Lymphocytes, Genetic Vectors, Gene Expression, Mice, SCID, Immunotherapy, Adoptive, Mice, Antigens, Neoplasm, Cell Line, Tumor, Drug Discovery, Genetics, Animals, Humans, Molecular Biology, Pharmacology, Mice, Inbred ICR, Brain Neoplasms, Receptor, EphA2, Bystander Effect, Glioma, Survival Analysis, Retroviridae, Molecular Medicine

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    95
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
95
Top 1%
Top 10%
Top 10%
hybrid