CAR-NK Cell Development Services

NK cells are being explored as an alternative platform for CAR engineering and are recognized as an important player in the next generation of cellular therapies targeting cancer. Creative Biogene focuses on the total solution of CDMO services for cell therapy, and has established a fully closed cell process development platform, which can provide high-quality CAR-NK cell development services to customers with different demands.

Advantages of CAR-NK Cell Therapy

With the remarkable success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of hematologic malignancies, interest in developing CAR-engineered NK (CAR-NK) cells for cancer therapy is growing rapidly. CAR NK cell therapies have a strong potential to control tumor growth, showing resistance to conventional immunotherapy. CAR-NK therapies offer significant advantages over CAR-T therapies, such as:

Better safety, such as a lack or minimal cytokine release syndrome and neurotoxicity in autologous setting and graft-versus-host disease in allogenic setting.
Multiple mechanisms for activating cytotoxic activity. CAR-NK can inhibit cancer cells through multiple receptor recognition with higher sensitivity.
High feasibility for 'off-the-shelf' manufacturing. CAR-NK cells could be engineered to target diverse antigens, ultimately achieve an effective anti-tumo response.

Fig. 1 Generation process of CAR-NK cells. (Marofi, F. et al., 2021)

Our Services

The production protocols of CAR-NK cells largely overlap with those developed for CAR-T cells. NK cells need to incorporate a DNA strand with a prepared template for the CAR construct. When compared with CAR-Ts, consider alternative sources of vehicle cells and the need for their further expansion and activation. Creative Biogene has extensive experience in CAR-NK cell development, and we can provide comprehensive solutions in the following cell lifecycle development processes:

scFv and CAR Design

Among the structures of CARs, the antigen recognition structural domain (scFv) determines the specific recognition of CAR-T cells and is the critical structural domain. CAR enables NK cells to recognize and kill tumor cells by specific target antigens expressed on the surface of malignant cells. With our advanced antigen preparation platform, immunology platform, B-cell cloning platform, antibody development platform and scFv optimization platform, Creative Biogene is dedicated to constructing highly specific scFv for our customers, thus helping them to obtain CAR sequences with low side effects and high killing effect.

NK Cell Collection and Characterization

Sources of NK cells typically include peripheral blood (PB), umbilical cord blood (UCB), natural killer (NK) cell lines and stem cell-derived NK cells. Creative Biogene utilizes our advanced technology to isolate NK cells in combination with cell surface markers. We are committed to applying our expertise to ensure efficient isolation of NK cells and removal of contaminants to obtain high quality NK cells for subsequent development processes.

NK cell Activation and Expansion

NK cell activation and amplification contribute to efficient NK cell transduction. Creative Biogene utilizes highly pure and active GMP-grade cytokines to achieve efficient in vitro expansion of NK cells. These cytokines include IL-2, IL-7, IL-12, IL-15 and IL-21.

Transfection or Transduction Vectors for CAR

The methods used for transduction of CARs into T cells are also applicable in NK cells. With advances in gene modification technology, many methods are being used to generate CAR-NK. Creative Biogene uses mainly lentiviral or retroviral based transduction methods for stable and efficient transduction of CAR genes into NK cells.

CAR-NK Cell Quality Control and Functional Testing

Creative Biogene is committed to providing high quality CAR-NK cell development services to our clients. We are dedicated to providing comprehensive quality control and testing services throughout the CAR-NK development process, including but not limited to the following tests.

Category	Testing Content
General Testing	Appearance, pH, molar concentration of osmolality
Cell Characterization/Functional Assays	Cell number, cell viability, NK cell purity, CAR positive rate, immune cell composition, cytokine secretion, cell killing
Impurity Detection	Culture process additive residue, magnetic bead residue
Safety Testing	CAR gene copy number, bacterial endotoxin detection, sterility testing, mycoplasma detection, RCL

Production Process

Creative Biogene offers fully integrated solutions for CAR-NK cell development. Our one-stop development process helps our clients accelerate the development of CAR-NK cell therapies.

Production Process

As a leading provider of CDMO services in the biopharmaceutical sector, Creative Biogene is committed to providing customized CAR-NK cell development services to help our clients accelerate their development process. Please feel free to contact us if you have a need, and our experienced specialists will be happy to assist you.

Reference:

Marofi, F. et al. CAR‐NK cell in cancer immunotherapy; A promising frontier. Cancer Science, 2021, 112(9): 3427-3436.

* For research use only. Not intended for any clinical use.

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