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Co-Stim CAR Design Service

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

CAR and Co-stimulatory

The Chimeric Antigen Receptor (CAR) consists of several integral parts that bridge antigen recognition to T cell signaling, driving T cell activation following ligation of the CAR. The structure of a second-generation CAR includes an extracellular domain, a transmembrane domain, and an intracellular domain. The T cell activation domain and co-stimulatory domain are located within the intracellular domain. The co-stimulatory domain is crucial for T cell expansion, IL-2 production, evasion of T cell anergy, and apoptosis. The choice of co-stimulatory domain in CAR design can impact T cell differentiation, persistence, anti-tumor response kinetics, and toxicity profiles. Different co-stimulatory molecules may result in varying therapeutic outcomes. Ongoing research focuses on exploring novel co-stimulatory molecules, combinations of multiple co-stimulatory domains, and understanding the crosstalk between CAR-driven and endogenous co-stimulatory pathways to enhance CAR-T cell therapy efficacy.

Fig.1 The structure of traditional CAR. (Honikel, M. M., & Olejniczak, S. H., 2022)Fig 1. The structure of a second-generation CAR.1

Co-Stim CAR Design at Creative Biolabs

In traditional CAR-T cells, the intracellular domain contains signaling 1 and signaling 2 domains, which activate the T cell receptor (TCR) and co-stimulatory pathways of the T cell, respectively. Signal 1 is delivered primarily by the intracellular domain of the CAR and activates the proliferation and killing of T cells. Traditional CAR-T cells contain only one CAR structure, which is responsible for recognizing tumor cells and delivering signal 1.

In co-stim CAR-T cells, the natural TCR (T-cell receptor) is retained. In addition to the CAR structure, the natural TCR recognizes and transmits Signal 1, while the co-stimulatory CAR structure is introduced, which transmits Signal 2. Signal 1 is mainly transmitted by the intracellular domain of the TCR, while signal 2 is mainly transmitted by the intracellular domain of the co-stimulatory CAR. Co-stimulation of CAR-T cells can activate the proliferation and killing functions of T cells at the same time, as well as enhance the anti-tumor effect.

Fig.2 Co-stim CAR-T cells. (Creative Biolabs Original)

By preserving the natural TCR and introducing a co-stimulatory CAR, co-stim CAR-T cells can recognize and kill tumor cells more efficiently with fewer side effects.

More about Co-Stim CAR

  • What is the key point of co-stim CAR design?
    By preserving the natural T-cell signaling pathway, co-stim CAR-T cell avoids over-activation and reduces the risk of serious side effects, such as cytokine release syndrome.
  • What are the advantages of co-stim CAR?
    Compared to other CAR-T technologies, the co-stim CAR-T technology has significant advantages in therapeutic efficacy and safety.
    • Co-stim CAR-T cells utilize the broad recognition ability of natural TCR and combine it with the signaling pathway of the co-stimulatory CAR to more effectively identify and kill tumor cells, improving therapeutic efficacy. Due to the broad recognition ability, co-stim CAR-T cells can recognize multiple tumor antigens. Even if tumor cells escape antigens, they can still be identified and killed through other antigens, improving the durability of treatment.
    • Co-stim CAR-T cells retain the signaling pathway of natural TCR, which can avoid excessive activation, reduce off-target toxicity, and improve treatment safety.

Co-stim CAR has broad application prospects and is expected to become an important weapon in the field of cancer treatment in the future. Creative Biolabs is dedicated to helping researchers design more effective CAR-T cells. Please feel free to contact us.

Reference

  1. Honikel, M. M., & Olejniczak, S. H. " Co-Stimulatory Receptor Signaling in CAR-T Cells. " Biomolecules 12.9 (2022): 1303.
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