TY  - CONF
A1  - Zhang, Congcong
A1  - Burger, Michael Christian
A1  - Schönfeld, Kurt
A1  - Genβler, Sabrina
A1  - Sahm, Christiane
A1  - Naundorf, Sonja
A1  - Odendahl, Marcus
A1  - Nowakowska, Paulina
A1  - Tonn, Torsten
A1  - Grez, Manuel
A1  - Steinbach, Joachim Peter
A1  - Wels, Winfried
T1  - ErbB2/HER2-specific NK cells for adoptive cancer immunotherapy
T2  - Journal for ImmunoTherapy of Cancer : official journal of the Society for Immunotherapy of Cancer (SITC)
N2  - Poster presentation: 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)
Significant progress has been made over the last decade towards realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells, and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also continuously expanding cytotoxic cell lines such as NK-92 are being considered for adoptive cancer immunotherapy. High cytotoxicity of NK-92 has previously been shown against malignant cells of hematologic origin in preclinical studies, and general safety of infusion of NK-92 cells has been established in phase I clinical trials. To enhance their therapeutic utility, we genetically modified NK-92 cells to express chimeric antigen receptors (CAR) specific for tumor-associated surface antigens. Such CAR were composed of a tumor-specific scFv antibody fragment fused via hinge and transmembrane domains to intracellular signaling moieties such as CD3 zeta chain, or composite fusion molecules also containing a costimulatory protein domain in addition to CD3 zeta. For development towards clinical applications, here a codon-optimized second generation CAR was constructed that consists of an ErbB2-specific scFv antibody domain fused via a linker to a composite CD28-CD3 zeta signaling domain. GMP-compliant protocols for vector production, lentiviral transduction and expansion of a genetically modified NK-92 single cell clone (NK-92/5.28.z) were established. Functional analysis of NK-92/5.28.z cells revealed high and stable CAR expression, selective cytotoxicity against ErbB2-expressing but otherwise NK-resistant tumor cells of different origins in vitro, as well as homing to ErbB2-expressing tumors in vivo. Furthermore, antigen specificity and selective cytotoxicity of these cells were retained in vivo, resulting in antitumoral activity against subcutaneous and intracranial glioblastoma xenografts in NSG mice. Ongoing work now focuses on the development of these cells for adoptive immunotherapy of ErbB2-positive glioblastoma.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/32416
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-324166
SN  - 2051-1426
N1  - © 2013 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
VL  - 1
IS  - (Suppl 1):P38
PB  - BioMed Central
CY  - London
ER  -