Ambrose, Christine, Su, Lihe, Wu, Lan, Dufort, Fay J., Sanford, Thomas, Birt, Alyssa, Hackel, Benjamin J., Hombach, Andreas ORCID: 0000-0001-9328-8442, Abken, Hinrich, Lobb, Roy R. and Rennert, Paul D. (2021). Anti-CD19 CAR T cells potently redirected to kill solid tumor cells. PLoS One, 16 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Successful CAR T cell therapy for the treatment of solid tumors requires exemplary CAR T cell expansion, persistence and fitness, and the ability to target tumor antigens safely. Here we address this constellation of critical attributes for successful cellular therapy by using integrated technologies that simplify development and derisk clinical translation. We have developed a CAR-CD19 T cell that secretes a CD19-anti-Her2 bridging protein. This cell therapy strategy exploits the ability of CD19-targeting CAR T cells to interact with CD19 on normal B cells to drive expansion, persistence and fitness. The secreted bridging protein potently binds to Her2-positive tumor cells, mediating CAR-CD19 T cell cytotoxicity in vitro and in vivo. Because of its short half-life, the secreted bridging protein will selectively accumulate at the site of highest antigen expression, ie. at the tumor. Bridging proteins that bind to multiple different tumor antigens have been created. Therefore, antigen-bridging CAR-CD19 T cells incorporate critical attributes for successful solid tumor cell therapy. This platform can be exploited to attack tumor antigens on any cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ambrose, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Su, LiheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, LanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dufort, Fay J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanford, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Birt, AlyssaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hackel, Benjamin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hombach, AndreasUNSPECIFIEDorcid.org/0000-0001-9328-8442UNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lobb, Roy R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rennert, Paul D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-586859
DOI: 10.1371/journal.pone.0247701
Journal or Publication Title: PLoS One
Volume: 16
Number: 3
Date: 2021
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHIMERIC ANTIGEN RECEPTOR; B-CELLS; THERAPY; IMMUNOTHERAPY; ACTIVATION; CD19; LEUKEMIA; GLIOBLASTOMA; EXPRESSION; ANTIBODIESMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58685

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