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Current adoptive immunotherapy using NK cells has become a promising approach for the treatment of multiple malignancies. However, most of these trials use primary NK cells isolated from peripheral or cord blood which can have donor-dependent variability and can be challenging to genetic engineers to improve antitumor functions, leading to manufacturing issues related to expansion and storage. Induced pluripotent stem cells (iPSCs) offer an off-the-shelf alternative NK cell source for adoptive NK cell therapy due to their homology, ease to genetically modification on a clonal level, and can be used as an unlimited source of NK cells. With the support of our unique NK cell engineering platform, Creative Biolabs provides a cell-based "off-the-shelf" NK cell bank for the next generation of NK-based cell therapies.
At Creative Biolabs, we provide a one-stop pipeline to manufacture iPSC-NK cells. In the iPSC stage, iPSC can be obtained from healthy donor tissues and genetically reprogrammed to improve anti-tumor activity. A single iPSC line can be designed with multiple components. The genetically optimized iPSC can be cryopreserved as a master cell bank to provide a consistent and unlimited source of NK cells.
Fig. 1 iPSC-NK cells manufacturing platform.
Although NK cells have promising functions for the treatment of cancer, these cells may become less effective over time due to the decrease in NK persistence and cytotoxicity. Therefore, genetic modification of iPSC-NK cells to overcome various limitations associated with NK therapy will prove to be useful for enhancing antigen specificity and cytotoxicity.
Editing in the pluripotent stage will result in a fully edited clone that can be completely distinguished into the NK lineage. At Creative Biolabs, we provide several strategies to improve the anti-tumor function of NK cells, including but not limited to:
a) Expressing a mutant form of the non-cleavable CD16 (hnCD16) to inhibit the cleavage of the ADAM17 protease. The fused cytokine receptor-ligand receptor exhibits enhanced ADCC for various tumor targets,
b) Expressing membrane-bound IL15 (mbIL15) to increase persistence, survival, and expansion in vivo.
Fig.2 Genetic modification strategies of iPSC-NK cells to enhance the effectiveness of NK-based cellular therapy.
Notably, as the leading cell therapeutics biotech that provides cell therapy related services, Creative Biolabs provides one-stop services for CAR-NK therapy development, including but not limited to:
If you are interested in our services, please send an email to contact us, and our team will get back to you as soon as possible.
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NEW SOLUTION
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Canine CAR-T Therapy Development: From early target discovery, CAR design and construction, cell culture, and transfection, to in vitro and in vivo function validation.
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