Natural killer (NK) cells are cytotoxic immune cells that play an important role in the defense against cancer. Genetic manipulation of NK cells to improve their persistence, tumor-targeting capacity, and the ability to home to disease sites in vivo may further enhance the efficacy of NK cell-based cancer immunotherapy. Armed with mature cell reprogramming platforms, Creative Biolabs provides customized NK cell reprogramming services by in vitro transcribed mRNA for worldwide customers.
NK cells are key regulators of T cell-mediated immunity, which supports the idea that NK cell immunotherapy may be an alternative or complementary to T cell immunotherapy. Various NK cell-based immunotherapy approaches are shown in Fig.1.
NK cells are considered ideal targets for adoptive transfer owing to their capability to eliminate tumor cells in a non-MHC and non-tumor antigen-restricted manner. The transfer of expanded and activated NK cells is increasingly used to improve NK cell responses. Autologous NK cells, allogenic NK cells, NK cell lines, or Chimeric Antigen Receptor (CAR) NK cells may be harnessed as a source of NK cells for adoptive transfer.
The activity of NK cells may be stimulated by cytokine treatment. IL-2, IL-15, IL-21 are the most interesting agents that potentiate NK cell activity.
Activating and inhibitory receptors or their ligands can be targeted by monoclonal antibody (mAb) to increase therapeutic NK cell activity. The most widely used strategy in cancer immunotherapy is to employ tumor-specific antibodies that promote antibody-dependent cellular cytotoxicity (ADCC) through the ligation of CD16 receptors on NK cells.
Blocking the inhibitory pathways dampening NK cell function in cancer is an encouraging strategy for NK cell immunotherapy. Targeting inhibitory receptors may release the antitumor potential of NK cells. Blocking antibodies directed against MICA boosts NK cell activity by preventing the shedding of soluble MICA and NKG2D downregulation. These inhibitory NK cell receptors or checkpoint proteins include but are not limited to programmed death-1 (PD-1)/PD-L1, TIM-3, CD96, or T cell immunoreceptor with Ig and ITIM domains (TIGIT), Killer cell Immunoglobulin-like Receptors (KIRs), NK Group 2A (NKG2A).
Fig.1 Current NK cell-based immunotherapy to treat metastatic cancer. (Lorenzo-Herrero, 2019)
Introducing genes into NK cells that improve their in vivo viability, cytotoxicity, and ability to home to disease sites could improve the efficacy of NK cell-based immunotherapy. mRNA electroporation is an alternative method to genetically modify NK cells without using viral vectors, precluding the need for high-level biosafety laboratories.
NK cells can be genetically reprogrammed efficiently using mRNA electroporation method that induces rapid and reproducible transgene expression in nearly all transfected cells, without negatively influencing their viability, phenotype, and cytotoxic function. For instance, electroporation of NK cells with mRNA coding for the chemokine receptor CCR7 significantly promoted migration toward the lymph node-associated chemokine CCL19. Furthermore, introduction of mRNA encoding the high-affinity antibody-binding receptor CD16 significantly enhanced NK cell cytotoxicity against antibody drug-coated lymphoma cells.
Electroporation of NK cells with various mRNAs can be used to genetically modify multiple patterns of NK cells in an efficient manner. It has the potential to improve multiple aspects of its in vivo tumor targeting to develop more effective adoptive NK cell cancer immunotherapies. The general steps are summarized below.
Our custom reprogramming and characterization services empower you to focus on your research interests. Simply send us your donor cells and we'll use our cutting-edge reprogramming technologies to produce induced NK cells within a short time. Once you receive the cell products from us, our dedicated specialists will share their expertise and provide ongoing support to help ease the adaptation of the cells into your experimental systems.
Our NK cells reprogramming services can be tailored to meet your experimental requirements, helping you to save time and resources. If you are interested in our customized NK cells reprogramming by mRNA, please feel free to contact us for more information.
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