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45-1 Ramsey Road, Shirley, NY 11967, USA
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Four Generations CAR Development

As a leading technology provider, Creative Biolabs has established a solid platform for offering a variety of CAR products. Our brilliant scientists can design tailor-made solutions to fit your exact needs, which can greatly assist your research, preclinical investigation and early stage clinical studies.

A chimeric antigen receptor (CAR) mainly consists of a single chain variable fragment (scFv) from a mAb, an extracellular hinge and spacer element, a transmembrane region (TM) and an internal signaling domain such as CD3ζ or Fc receptor γ cytoplasmic signaling domains (FcεRIγ). The main advantage of CAR modified T cell is that it decreases MHC restriction, which allows the adoptive immune cells to be directly activated in various types of cancers.

Four Generations CAR Development

Mackall CL, Merchant MS, Fry TJ. Immune-based therapies for childhood cancer. Nat Rev Clin Oncol. 2014 Dec;11(12):693-703.

The component of co-stimulatory endodomain classifies different CAR generations. The first generation of CAR usually consists of a scFv (blue region) which binds a specific antigen, a TM (black region) and a signaling domain like CD3ζ (red region). The second generation of CAR is designed by inserting a co-stimulatory endodomain such as 4-1BB or CD28 (pink region or green region) between the scFv and the signaling domain. The third generation of CAR has two co-stimulatory endodomains inserted between the scFv and the signaling domain. In comparison with the ones without the co-stimulatory endodomain, CARs with co-stimulatory domains have been demonstrated to have elevated expansion and persistence.

A scFv domain includes a single heavy chain variable fragment which is fused to a single light chain variable fragment via a flexible linker. It is specific to tumor-associated antigens. With many years of experience, we can construct scFvs derived from murine or humanized antibodies originate from phage display antibody library (immune, naïve, and synthetic).

Most CARs have an extracellular hinge and spacer domain which connects the antigen binding region and the transmembrane region together. The same scFv with different linkers can enable the CAR engrafted T cells with different killing efficiencies. Creative Biolabs can construct spacer element with high quality which makes scFv to be more flexible and accessible, so as to ensure the CARs products the highest efficiency in killing cancer cells.

Our elite scientists have cloned the intracellular signaling domain from T cell receptor (TCR) ζ chain (CD3ζ) or Fc receptor γ cytoplasmic signaling domains (FcεRIγ). In addition, we have also generated a wide range of costimulatory domains from different molecules, such as CD28, CD137 (4-1BB), CD134 (OX40) and DAP10.

With years of experiences and sufficient researches, Creative Biolabs has successfully developed various CARs products. Our rigorous quality control guarantees that we offer the best service to satisfy your specific requirements.

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CONTACT US

USA
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-871-5806
Fax: 1-631-207-8356
Email:

Europe
Ringstrasse 4, 64401 Gross-Bieberau, Germany
Tel: 44-207-048-3343

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