Universität zu Köln

Martyniszyn, Alexandra, Krahl, Ann-Christin, Andre, Maya C., Hombach, Andreas A. and Abken, Hinrich (2017). CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies. Hum. Gene Ther., 28 (12). S. 1147 - 1158. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-7422

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Abstract

The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients, with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells that lack the CAR targeted antigen. In this situation, a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T-cell response upon engagement of CD19 or CD20 on target cells showing a true `` OR'' gate recognition in redirecting T-cell activation. T cells with the anti-CD20-CD19 CAR efficiently killed patients' chronic lymphocytic leukemia cells in vitro. The bispecific CAR T cells cleared pediatric acute lymphocytic leukemia with a mixed CD19+ CD20+/CD20-phenotype from the blood and bone marrow of transplanted mice, while anti-CD20 CAR T cells left CD20-leukemic cells behind without curing the disease. Data indicate the superior anti-leukemic activity in the control of leukemia, implying that the anti-CD20-CD19 bispecific CAR T cells may reduce the risk of relapse through antigen-loss leukemic cells in the long term.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Martyniszyn, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Krahl, Ann-Christin UNSPECIFIED UNSPECIFIED UNSPECIFIED Andre, Maya C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-208917
DOI:	10.1089/hum.2017.126
Journal or Publication Title:	Hum. Gene Ther.
Volume:	28
Number:	12
Page Range:	S. 1147 - 1158
Date:	2017
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	1557-7422
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MODIFIED DENDRITIC CELLS; GENE-THERAPY; CANCER-IMMUNOTHERAPY; ONCOLYTIC VIRUSES; MELANOMA; COMBINATIONS; CRISPR-CAS9; VACCINES; IMMUNITY; GLIOMA Multiple languages Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20891