CAR-NK Vector Design and Construction

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Although chimeric antigen receptor (CAR) engineered T (CAR-T) cells have achieved significant success in the treatment of hematological malignancies, the interest in CAR-transduced NK cells (CAR-NK) has rapidly increased due to the limited number of T cells. Compared with CAR-T cells, CAR-NK cells have many advantages, such as the safety of clinical use, the mechanism of recognizing cancer cells, and the abundance in clinical samples. To avoid these obstacles, researchers are turning to natural killer (NK) cells to expand the application of CAR-directed therapy in patients with B-cell malignancies. As a leading cell therapeutics provider, Creative Biolabs supplies high-quality CellRapeutics™ CAR-NK vector construction service tailored to your special needs.

NK Cell-based CAR Design and Construction

So far, most CAR-NK cell studies have used CAR constructs designed for CAR-T cells. Recently, novel CAR constructs have been specifically designed for NK cells. These different CAR structures have different effects on the cytotoxicity and cytokines of NK cells.

Conventional CAR contains an antigen recognition domain (for example, ScFv or NKG2D), a transmembrane domain, and a signal transduction domain that provides signals to activate NK cells. The first-generation CAR only contains CD3ζ or DAP12 as the signaling domain, and CD3ζ seems to be a better signaling domain than DAP10, and DAP12 may activate NK cells better than CD3ζ. In contrast, the second-generation CAR and CD3ζ express the second signal domain (such as CD28 or 4-1BB) together. The third-generation CAR contains two costimulatory signal domains. Based on the mechanism by which NKG2D activates NK cells, a unique CAR structure was developed, which contains NKG2D as the extracellular domain and connects DAP10 and CD3ζ as key signal molecules. The connection of CAR clusters and their ligands induced by antigen binding or NKG2D triggers signal transduction, leading to NK cell activation, cytotoxicity to cancer cells, cytokine production, survival, and proliferation.

Basic principle of CAR-NK cells

Fig.1 Basic principle of CAR-NK cells. (Hu, 2018)

In addition to providing CAR design and cloning services for conventional three generations, Creative Biolabs also provides novel CAR design services to optimize your CAR-NK therapy development. You can explore more special CARs at CAR Design & Construction to find the product you are interested in.

CAR-NK Cell Generation

Unlike T cells, NK cells can be prepared in advance and can be conveniently used for a variety of patients on demand. Currently, Creative Biolabs provides readily available NK cells from a variety of sources, including NK92 cell line, PBMC, UBC, CD34 + hematopoietic progenitor cells (iPCC).

Sources and manufacturing of CAR-NK cell products.

Fig.2 Sources and manufacturing of CAR-NK cell products. (Xie, 2020)

One-Stop CAR-NK Development Services

With state-of-art CAR development platforms and advanced technologies, Creative Biolabs is capable of offering one-stop CAR-NK cell development services. Please contact us for more details.

Biomarker Identification & Selection

High Affinity ScFv Generation

Virus Packaging & CAR Gene Delivery

CAR-T In Vitro Assay

CAR-T Preclinical In Vivo Assay

CAR-T Clinical Trial

References

Xie, G., et al. (2020). CAR-NK cells: A promising cellular immunotherapy for cancer. EBioMedicine, 59, 102975.
Hu, Y., et al. (2018). Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacologica Sinica, 39(2), 167-176.