Universität zu Köln

Vyas, Maulik ORCID: 0000-0003-2996-4682, Schneider, Ann-Charlott, Shatnyeva, Olga, Reiners, Katrin S., Tawadros, Samir, Kloess, Stephan, Koehl, Ulrike, Hallek, Michael, Hansen, Hinrich P. and von Strandmann, Elke Pogge (2016). Mono- and dual-targeting triplebodies activate natural killer cells and have anti-tumor activity in vitro and in vivo against chronic lymphocytic leukemia. OncoImmunology, 5 (9). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

Full text not available from this repository.

Abstract

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia that affects B lymphocytes in adults. Natural killer (NK) cells in CLL patients are intrinsically potent but display poor in situ effector functions. NKG2D is an activating receptor found on NK and CD8(+) T cells and plays a role in immunosurveillance of CLL. In this study, we developed mono- and dual-targeting triplebodies utilizing a natural ligand for human NKG2D receptor (ULBP2) to retarget NK cells against tumor cells. Triplebodies in both formats showed better ability to induce NK-cell-dependent killing of target cells compared to bispecific counterparts. A mono-targeting triplebody ULBP2-aCD19-aCD19 successfully triggered NK cell effector functions against CLL cell line MEC1 and primary tumor cells in allogenic and autologous settings. Additionally, a dual-targeting triplebody ULBP2-aCD19-aCD33 specific for two distinct tumor-associated antigens was developed to target antigen loss variants, such as mixed lineage leukemia (MLL). Of note, this triplebody exhibited cytotoxic activity against CD19/CD33 double positive cells and retained its binding features even in the absence of one of the tumor antigens. Further, ULBP2-aCD19-aCD19 showed significant in vivo activity in immune-deficient (NSG) mouse model transplanted with CLL cell line as target cells and human immune cells as an effector population providing a proof-of-principle for this therapeutic concept.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vyas, Maulik UNSPECIFIED orcid.org/0000-0003-2996-4682 UNSPECIFIED Schneider, Ann-Charlott UNSPECIFIED UNSPECIFIED UNSPECIFIED Shatnyeva, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Reiners, Katrin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tawadros, Samir UNSPECIFIED UNSPECIFIED UNSPECIFIED Kloess, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehl, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Hinrich P. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Strandmann, Elke Pogge UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-288950
DOI:	10.1080/2162402X.2016.1211220
Journal or Publication Title:	OncoImmunology
Volume:	5
Number:	9
Date:	2016
Publisher:	TAYLOR & FRANCIS INC
Place of Publication:	PHILADELPHIA
ISSN:	2162-402X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language T-CELLS; NKG2D RECEPTOR; TUMOR-CELLS; NK CELLS; MULTIPLE-MYELOMA; ANTIGEN; GAMMA; CYTOTOXICITY; LIGANDS; LYSIS Multiple languages Oncology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28895