Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Ambrose, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Su, Lihe UNSPECIFIED UNSPECIFIED UNSPECIFIED Wu, Lan UNSPECIFIED UNSPECIFIED UNSPECIFIED Dufort, Fay J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanford, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Birt, Alyssa UNSPECIFIED UNSPECIFIED UNSPECIFIED Hackel, Benjamin J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas UNSPECIFIED orcid.org/0000-0001-9328-8442 UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Lobb, Roy R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rennert, Paul D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language CHIMERIC ANTIGEN RECEPTOR; B-CELLS; THERAPY; IMMUNOTHERAPY; ACTIVATION; CD19; LEUKEMIA; GLIOBLASTOMA; EXPRESSION; ANTIBODIES Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58685