As one of the most potential next great cancer immunotherapies, engineered natural killer (NK) cells which is inspired by CAR-T cells could be faster, safer and cheaper than CAR-T, also CAR-NK may work in situations where CAR-T cells falter. Now CAR-NK cell therapy discovery and development are at the very beginning, as a leading service provider for cancer immunotherapies, Creative Biolabs has established comprehensive integrated solutions for discovery and development regarding various cellular and gene therapies, including T Cell Receptor (TCR) T cell therapy, Chimeric Antigen Receptor (CAR) T Cell Therapy, CAR-NK cell therapy, CAR-macrophage cell therapy.

Fig.1 Natural killer cells (yellow) attack a cancer cell. (Source: Eye of Science)

Chimeric antigen receptors (CARs) contain an antigen recognition domain, a transmembrane domain and a signaling domain which can mediate the activation signaling of NK cells. Activated NK signaling will induce cell activation, survival and proliferation, cytokine production and cytotoxicity of NK cells against cancer cells (see Fig.2). The antigen recognition domain includes both single-chain variable fragment (scFv) specific for tumor antigen or NKG2D. We offer various types of CAR generations with different intracellular signaling domains including CD3ζ, DAP10 or DAP12, CD28, 4-1BB. We can design the most suitable CAR to fit your project.

Fig.2 The tumor microenvironment limits the functioning of CAR-T cells.¹

Among three types of NK cell adoptive transfer therapies (see Fig.3), CAR-NK has several appealing features. Firstly, it is engineered from ceaseless NK cells. Secondly, it is constructed with mutant NK92 cells. Lastly, better survival rates compared with other NK therapies. Creative Biolabs has developed a unique and professional platform for NK cell therapy covering all services and integrated solutions. You can flexibly start at any stage or integrate or can be provided with an end-to-end solution to fit your projects. Both engineering services for αβ T cell and γδ T cell derived from patients and normal populations can be achieved. We are committed to getting access to the world most complete and customized solution to develop your CAR-NK cell product candidate.

Neoantigen Identification

Empowered by comprehensive gene and protein analysis technologies, we provide unique de novo neoantigen discovery, identification and selection to get an appropriate CAR-NK therapy target with high affinity, and potency.

scFv Generation and Optimization

We provide a wide range of antibody database and libraries derived from different species such as mouse, rabbit and human to help screen the suitable antibodies for specific antigens. In addition, we offer affinity measurement and optimization platform, to help generate the scFv candidate for next step CAR construction.

CAR Design & Construction

Then we will provide the CAR design and construction which is the key technology for CAR-NK cell therapy. A broad range of CAR technologies are available at Creative Biolabs, including but not limited to: suicide CAR, inducible CAR, enhanced CAR, bispecific CAR, synNotch CAR, masked CAR, oxygen-sensing CAR etc.

CAR-NK Preparation

Engineered CAR-NK cells will be prepared for further in vitro and in vivo assays with various transfection technologies including electroporation, as well as cell transduction though adenovirus, lentivirus retroviral, etc. To meet your different requirements, both GLP and GMP production can be achieved. During NK preparation, both genetic manipulation and NK cell manipulation can be designed.

CAR-NK In Vitro Validation

For generated CAR-NK products, a full spectrum of in vitro assays is available to evaluate the efficiency of CAR-NK cell therapy product, including CAR expression validation, CAR-NK cell proliferation, cytokine release assay, cytotoxicity assay, etc.

CAR-NK In Vivo Testing

After conducting a series of in vitro assays, various in vivo testing systems will be utilized to assess the CAR-NK product, such as animal models, efficacy testing, biodistribution studies, toxicology evaluation and other GLP compliant assays.

Fig.3 End-to-end CAR-NK Integrated Solutions.

Highlights of Our CAR-NK Therapy Program

With 100% guarantees for quality and dedication that has been approved by our clients, Creative Biolabs is committed to helping you get access to the world most complete solution for your CAR-NK product candidate. Our extensive expertise and advanced platform will ensure a great asset to promote the progression to launch the clinical trials. For more detailed information or a quote, please don’t hesitate to contact us.

Reference

1. Kowalczyk, Adrian, et al. "Chimeric Antigen Receptor T Cell and Chimeric Antigen Receptor NK Cell Therapy in Pediatric and Adult High-Grade Glioma—Recent Advances." Cancers 16.3 (2024): 623.

For Research Use Only | Not For Clinical Use