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

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 mole...

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Bibliographic Details
Published in:Molecular therapy 2015-01, Vol.23 (1), p.171-178
Main Authors: Iwahori, Kota, Kakarla, Sunitha, Velasquez, Mireya P, Yu, Feng, Yi, Zongzhen, Gerken, Claudia, Song, Xiao-Tong, Gottschalk, Stephen
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Brain Neoplasms - immunology
Brain Neoplasms - mortality
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Bystander Effect - immunology
Cancer
CD3 Complex - genetics
CD3 Complex - immunology
Cell culture
Cell Line, Tumor
Gene Expression
Gene therapy
Genetic Vectors
Glioma - genetics
Glioma - immunology
Glioma - pathology
Glioma - therapy
Humans
Immunotherapy
Immunotherapy, Adoptive - methods
Kinases
Lung Neoplasms - immunology
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Lung Neoplasms - therapy
Lymphocytes
Male
Medical schools
Medicine
Mice
Mice, Inbred ICR
Mice, SCID
Original
Receptor, EphA2 - genetics
Receptor, EphA2 - immunology
Retroviridae - genetics
Survival Analysis
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Tumors
Xenograft Model Antitumor Assays
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Description
Summary: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.
ISSN:1525-0016
1525-0024
DOI:10.1038/mt.2014.156