Chimeric Antigen Receptor (CAR) NK Cell Design and Manufacturing Service
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CAR-NK cell therapy represents a leap forward in cancer immunotherapy. CAR-NK cell therapy targets limitations present in CAR-T therapies by harnessing the inherent cytotoxic activity of NK cells and complementing it with CAR technology. CAR-NK cells are very safe and effective, and associated side effects like cytokine release syndrome (CRS) and neurotoxicity are less likely to occur, especially in an allogeneic fashion. Creative Biolabs has led this trend, providing an entire service suite in CAR-NK cell design, engineering, and manufacturing to meet the evolving needs of cancer therapies. This dedication to delivering exceptional, bespoke solutions allows Creative Biolabs to collaborate with scientists, biotech companies, and pharmaceutical companies to develop CAR-NK cell therapies from the laboratory into the clinic.
Introduction
CAR-NK cells are engineered with chimeric antigen receptors (CARs) composed of three critical regions: an antigen recognition region, a transmembrane region, and a signaling region. These CAR components enable NK cells to recognize and attack cancer cells effectively. The antigen recognition domain typically includes single-chain variable fragments (scFv) specific to tumor antigens or NKG2D ligands. With various CAR designs, including CD3ζ, DAP10, and CD28 intracellular signaling domains, Creative Biolabs ensures the optimal CAR configuration for each unique application.
Fig.1 The Overview of The Constructs and Targets of CAR-NK Cells.1
Innovative CAR Technologies
Bispecific and Multispecific CARs
Bispecific and multispecific CARs are engineered to target several tumor antigens simultaneously, addressing tumor heterogeneity and reducing immune evasion. Creative Biolabs integrates multiple binding domains within a single CAR construct, enhancing tumor cell recognition and destruction, especially for tumors with diverse antigen expression.
Oxygen-Sensing CARs
To tackle the low-oxygen environments typical of solid tumors, oxygen-sensing CARs activate under hypoxic conditions. This feature enables CAR-NK cells to maintain cytotoxic activity in otherwise challenging tumor microenvironments, helping sustain the therapy's effectiveness where other treatments may lose impact.
SynNotch and Masked CARs
SynNotch CARs provide targeted activation by recognizing antigen sequences, activating only upon detection of specific antigen combinations, thus reducing off-target effects. Masked CARs, designed to be inactive until reaching the tumor site, further safeguard healthy tissues from unintended cytotoxicity, making these CARs highly suitable for precision therapies in solid tumors.
Affinity Tuning and Humanization
Affinity tuning optimizes CAR-NK cells' binding strength to tumor antigens, ensuring high specificity and minimal off-target interactions. Humanization services adapt CARs to the patient's immune profile, reducing immunogenicity and improving compatibility for more effective tumor targeting and prolonged therapeutic efficacy. (see TCR and CAR optimization)
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Featured Workflow
Among three types of NK cell adoptive transfer therapies, 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's most complete and customized solution to develop your CAR-NK cell product candidate.
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.
We provide a wide range of antibody databases and libraries derived from different species such as mice, rabbits, and humans 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 the next step of CAR 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 is 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 through adenovirus, lentivirus retroviral, etc. To meet your different requirements, both GLP and compliant production can be achieved. During NK preparation, both genetic manipulation and NK cell manipulation can be designed.
For generated CAR-NK products, a full spectrum of in vitro assays is available to evaluate the efficiency of CAR-NK cell therapy products, including CAR expression validation, CAR-NK cell proliferation, cytokine release assay, cytotoxicity assay, etc.
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.
Why Choose Us?
Applications
Application Area
Details
Example Tumor Types
Hematologic Malignancies
CAR-NK cells demonstrate strong efficacy in blood cancers due to their ability to eliminate tumor cells in the bloodstream.
Multiple myeloma, leukemia, lymphoma
Solid Tumors
CAR-NK cells can target solid tumors, particularly those resistant to CAR-T therapies, leveraging their flexibility in hypoxic environments.
HER2+ breast cancer, prostate cancer, lung cancer
Combination Therapies
CAR-NK cells are effective when combined with other therapies like immune checkpoint inhibitors (ICIs) and chemotherapy, amplifying anti-cancer responses.
Integration with existing therapies for broader applications
Infectious Disease Models
CAR-NK cells also have potential in infectious disease research, aiding in the clearance of infected cells.
Hepatitis B and C, HIV
Autoimmune Conditions
Investigational use of CAR-NK cells in controlling autoimmune responses by selectively targeting immune cells involved in inflammation.
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
Zhang, Leisheng, et al. "CAR-NK cells for cancer immunotherapy: from bench to bedside." Biomarker Research 10.1 (2022): 12. Distributed under Open Access license CC BY 4.0, without modification.
Fig.1 The Overview of The Constructs and Targets of CAR-NK Cells.1
Fig.2 End-to-end CAR-NK Integrated Solutions. (Creative Biolabs Original)
T Cell Receptor (TCR) T Cell Therapy
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