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Chemically Programmed Switch CAR Construction Service

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

As a star therapy for cancer immunotherapy, CAR-T cell therapy has aroused eager attention from scientists to doctors to the public as soon as it came out, bringing hope for the cure of cancer patients. Although CAR-T cell therapy has a significant effect on the clinical treatment of hematological tumors, it is accompanied by serious side effects due to its uncontrollable activity. Currently, CAR-Ts face two key challenges. First, Good Manufacturing Practice (GMP) of CAR-T production is logically challenging. Strict manufacturing and shipping conditions are required when involving the collection, activation, transduction, expansion, cryopreservation, and infusion of autologous T cells. Second, CAR-Ts as a living drug can persist in cancer patients for a long time, and may even exist forever. FDA approved CAR-T is not equipped with safety switches to prevent or reduce target-tumor and target-non-tumor toxicity, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

In order to improve its controllability and safety, switch CAR-T came into being as a new generation of "intelligent" CAR-T cell therapy products, and further, Creative Biolabs has developed an innovative switch CAR-T platform controlled by small chemical molecules that aims to further precisely direct CAR to target cells, thereby addressing a major obstacle to this emerging therapeutic class.

Chemically Programmed Switch CAR Design

This Switch CAR design includes two basic components. One component is a catalytically-programmed Fab (cp-Fab) that can specifically couple small chemical molecules. As a switch molecule, Fab itself does not target any antigen, but the Fab fragment has a lysine residue at its hapten binding site that can be used to covalently bind the molecule or peptide of interest as a switch. The other component is the generic CAR-T, which does not target any antigens in humans. This generic CAR-T cell is produced by lentivirus transfection of human primary T cells.

The Fab fusion expresses a polypeptide fragment targeting a generic CAR, which is used to recruit CAR-T cells, while small molecules targeting tumor cells are directly coupled to Fab fragments. Only through programming (coupling) of small molecule compounds can Fab issue instructions as a switch molecule to precisely guide and activate CAR-T cells to specifically attack tumor cells. Therefore, when the switch molecule does not exist or is not programmed by chemical small molecules, CAR-T cells will not be activated to target tumor cells, thereby making CAR-T cells more controllable and safer.

Schematic representation of the chemical small molecule programming-controlled switch CAR-T.

Fig.1 Schematic representation of the chemical small molecule programming-controlled switch CAR-T. (Qi, 2020)

One-stop Switch CAR Development Services

With state-of-art CAR development platforms and advanced technologies, Creative Biolabs is capable of offering CAR-T-cell development services. For the regular or custom CAR backbone construction, please refer to our related services: CAR Design & Construction. To further assess your switch CAR biological efficacy (e.g., cytokine production, tumor killing, and CAR-T cell proliferation), our scientists can also provide comprehensive downstream services to complete your whole research. Please click CAR Cell In Vitro Assay Service, CAR-T Preclinical In Vivo Assay for more details.

Chemically Programmed Switch CAR Construction Service

For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Qi, J., et al. (2020). Chemically programmable and switchable CAR‐T therapy. Angewandte Chemie International Edition.
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