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- Title
NK-92: an 'off-the-shelf therapeutic' for adoptive natural killer cell-based cancer immunotherapy.
- Authors
Suck, Garnet; Odendahl, Marcus; Nowakowska, Paulina; Seidl, Christian; Wels, Winfried; Klingemann, Hans; Tonn, Torsten
- 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.
- Subjects
KILLER cells; CANCER immunotherapy; CELL lines; CLINICAL trials; CRYOPRESERVATION of organs, tissues, etc.
- Publication
Cancer Immunology, Immunotherapy, 2016, Vol 65, Issue 4, p485
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-015-1761-x