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One-stop UniCAR-NK Therapy Development

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

The antigen-specific redirection of T cells with chimeric antigen receptors (CARs) shows high therapeutic potential for targeting hematological malignancies. However, the production of CAR T cells still requires an extensive manufacturing process. Natural killer (NK) cells provide a promising alternative to produce CAR-modified effector cells in a GMP-compliant and cost-effective manner. Unlike T cells, primary NK cells and the NK cell line NK-92 can be used as ready-made products of allogeneic species, with a reduced risk of toxicity.

Creative Biolabs has established a modular universal CAR (UniCAR) platform, which cannot directly recognize the target antigen but will be redirected by the tumor-specific target module (Adaptor). The adaptor contains an antigen binding portion fused to the peptide epitope recognized by the UniCAR molecule, thereby allowing on/off switching of CAR activity, and promoting flexible targeting of various tumor antigens according to the presence and specificity of the adaptor.

Principle of UniCAR-NK System

UniCAR NK cells represent a universal off-the-shelf platform that is highly efficient and flexible and allowing the use of different adaptor formats for specific tumor targeting. UniCAR-NK cells can be generated using our adaptor CAR (AdCAR) system. AdCAR is designed to against a variety of surface antigens, which can be biotinylated antibodies, fusion proteins, Fab, svFv, nanobodies, and small molecules, or any neoepitope against tumor cell surface antigens (For more details about our uniCAR platform, please visit: Universal CAR Construction Service). NK cells were then engineered by transferring the plasmid encoding the AdCAR construct containing the NK cell costimulatory domain.

Schematic representation of AdCAR NK-92 function and structure. Fig.1 Schematic representation of AdCAR NK-92 function and structure. (Grote, 2020)

Conventional CARs versus UniCARs

One of the limitations of currently used CAR T cells is their lack of regulation. In particular, if there are no life-threatening side effects, CAR T cells cannot be shut down urgently. In addition, targeting tumor-associated antigens (TAA) to tumor cells or important tissues requires repeated switching on and off of CAR T cells. Compared to conventional CARs, UniCARs show several significant advantages, which is expected to overcome these limitations of conventional CAR:

1) UniCAR T cells can be easily regulated by the adaptor: just infusion of the adaptor they can be repeatedly "turned on", and by stopping the infusion followed by elimination of the adaptor to turn it "off".

2) The adaptor can reach the target quickly (for example, by spreading from the blood to the tumor)

3) The adaptor and UniCAR form a complex that can dissociate quickly (high Off rate)

One-stop UniCAR-NK Therapy Development

As the leading cell therapeutics biotech that provides cell therapy related services, Creative Biolabs provides one-stop services for UniCAR-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.

Reference

  1. Grote, S., et al. (2020). Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting. OncoImmunology, 9(1), 1825177.

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

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

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