T cells expressing CD19-specific Engager Molecules for the Immunotherapy of CD19-positive Malignancies.

Details

Serval ID
serval:BIB_9D7A98D4E846
Type
Article: article from journal or magazin.
Collection
Publications
Title
T cells expressing CD19-specific Engager Molecules for the Immunotherapy of CD19-positive Malignancies.
Journal
Scientific reports
Author(s)
Velasquez M.P., Torres D., Iwahori K., Kakarla S., Arber C., Rodriguez-Cruz T., Szoor A., Bonifant C.L., Gerken C., Cooper L.J., Song X.T., Gottschalk S.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
03/06/2016
Peer-reviewed
Oui
Volume
6
Pages
27130
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
T cells expressing chimeric antigen receptors (CARs) or the infusion of bispecific T-cell engagers (BITEs) have shown antitumor activity in humans for CD19-positive malignancies. While BITEs redirect the large reservoir of resident T cells to tumors, CAR T cells rely on significant in vivo expansion to exert antitumor activity. We have shown that it is feasible to modify T cells to secrete solid tumor antigen-specific BITEs, enabling T cells to redirect resident T cells to tumor cells. To adapt this approach to CD19-positive malignancies we now generated T cells expressing secretable, CD19-specific BITEs (CD19-ENG T cells). CD19-ENG T cells recognized tumor cells in an antigen-dependent manner as judged by cytokine production and tumor killing, and redirected bystander T cells to tumor cells. Infusion of CD19-ENG T cells resulted in regression of leukemia or lymphoma in xenograft models and a survival advantage in comparison to control mice. Genetically modified T cells expressing engager molecules may present a promising addition to current CD19-targeted immunotherapies.
Keywords
A549 Cells, Animals, Antigens, CD19/metabolism, Cell Line, Tumor, Cytotoxicity, Immunologic, Humans, Immunotherapy, K562 Cells, Mice, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy, Single-Chain Antibodies/genetics, Single-Chain Antibodies/metabolism, T-Lymphocytes/cytology, T-Lymphocytes/immunology, T-Lymphocytes/transplantation, Xenograft Model Antitumor Assays
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2019 10:54
Last modification date
02/11/2019 7:26
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