title: NK-92: an 'off-the-shelf therapeutic' for adoptive natural killer cell-based cancer immunotherapy.
abstract: Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however always remain variable due to individual differences of donors or patients. Long-term storage of clinical NK cell lots to allow repeated clinical applications remains an additional challenge. In contrast, the established and well-characterized cell line NK-92 can be easily and reproducibly expanded from a good manufacturing practice (GMP)-compliant cryopreserved master cell bank. Moreover, no cost-intensive cell purification methods are required. To date, NK-92 has been intensively studied. The cells displayed superior cytotoxicity against a number of tumor types tested, which was confirmed in preclinical mouse studies. Subsequent clinical testing demonstrated safety of NK-92 infusions even at high doses. Despite the phase I nature of the trials conducted so far, some efficacy was noted, particularly against lung tumors. Furthermore, to overcome tumor resistance and for specific targeting, NK-92 has been engineered to express a number of different chimeric antigen receptors (CARs), including targeting, for example, CD19 or CD20 (anti-B cell malignancies), CD38 (anti-myeloma) or human epidermal growth factor receptor 2 (HER2; ErbB2; anti-epithelial cancers). The concept of an NK cell line as an allogeneic cell therapeutic produced 'off-the-shelf' on demand holds great promise for the development of effective treatments.
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Berlin, Germany.
authors.forename: Garnet
authors.initials: G
authors.lastname: Suck
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Blasewitzer Strasse 68/70, 01307, Dresden, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Odendahl
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Württemberg-Hessen, Frankfurt am Main, Germany.
authors.forename: Paulina
authors.initials: P
authors.lastname: Nowakowska
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Württemberg-Hessen, Frankfurt am Main, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Seidl
authors.affiliation: Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt am Main, Germany.
authors.forename: Winfried S
authors.initials: WS
authors.lastname: Wels
authors.affiliation: NantKwest Inc, Culver City, CA, USA.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Klingemann
authors.affiliation: Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Blasewitzer Strasse 68/70, 01307, Dresden, Germany. t.tonn@blutspende.de.|Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Donation Service Baden-Württemberg-Hessen, Frankfurt am Main, Germany. t.tonn@blutspende.de.|Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. t.tonn@blutspende.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
keywords: CAR; Cellular immunotherapy; Clinical trial; NK cell line; NK-92; Tumor targeting