NK-92
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The NK-92 cell line is an
In clinical trials
Several phase 1 clinical trials have been performed by experts in the field of
Of the 39 patients enrolled across the three studies, 2 serious (grade 3–4) side-effects occurred during or after the infusion of NK-92 cells, the side effects disappeared afterward. The doses given to patients ranged from 1x108 cells/m2 to 1x1010 cells/m2 per infusion. Patients received between two and three infusions over a period of less than a week. About one-third of the treated patients had clinically meaningful responses with some of them fully recovering.
Comparison to other NK cells
In a 2017 study by Congcong Zhang and Winfried S. Wels, NK-92 cells were genetically engineered to recognize and kill specific human cancers by expressing
NK-92 cells, in contrast to NK-92 CAR-T cells, have predictable expansion kinetics and can be grown in bioreactors that produce billions of cells within a couple of weeks.
NK-92 variants
NK-92 cells, which require interleukin-2 (IL-2) for growth, have also been genetically altered with an IL-2 gene to allow them to grow in culture without the addition of IL-2.[12] They have also been engineered to express a high-affinity Fc-receptor which is the main receptor for monoclonal antibodies to bind to NK-92 and use their cytotoxic load to kill cancer cells.[13][14] The cells have been further engineered to express Chimeric Antigen Receptors (CARs) such as programmed death domain ligand 1 (PD-L1).[15] During the course of development, NK-92 cells were renamed activated NK cells (aNK) and the different variants have been designated as follows:
NK-92 = parental cells, later designated aNK
NK-92ci = NK-92 cells transfected with an episomal vector for expression of IL-2
NK-92 mi = NK-92 cells transfected with an MFG vector for expression of IL-2
haNK = NK-92 (aNK) transfected with a plasmid expressing high affinity CD16 FcR and erIL-2
taNK = NK-92 (aNK) transfected with either a plasmid or lentiviral vector expressing a CAR
t-haNK = NK-92 (aNK) transfected with a plasmid expressing a CAR and CD16 FcR erIL-2
qt-haNK = NK-92 (aNK) transfected with a plasmid expressing a 4th gene in addition to a CAR, the CD16 FcR, and erIL-2: examples: homing receptor of the CXCR family or immune-active cytokines
The high affinity Fc-receptor-expressing NK (haNK) cells were administered to patients with advanced Merkel cell carcinoma (MCC) and there were some notable responses. Currently, a HER2-targeted aNK (taNK) line and various t-haNK (CAR and Fc-receptor expressing) cell lines are in clinical trials in patients with various cancers, as described in the review “The NK-92 cell line 30 years later: its impact on natural killer cell research and treatment of cancer."[16]
Ownership and Licenses
Global rights to the NK-92 cell line were assigned to ImmunityBio Inc. (formerly NantKwest, Inc.). ImmunityBio's only authorized NK-92 distributor is Brink Biologics, Inc. (San Diego), which makes NK-92 cells and certain genetically modified CD16+ variants available to third parties for non-clinical research under a limited use license agreement.
References
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- ^ Fabian KP, Padget MR, Donahue RN, Solocinski K, Robbins Y, Allen CT (May 2020). "PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations". Journal for ImmunoTherapy of Cancer. 8 (1).
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Klingemann, H. (May 2023). "The NK-92 cell line-30 years later: its impact on natural killer cell research and treatment of cancer". Cytotherapy. 25 (5): 451–457.