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Chimeric T Cell Receptors (chTCR)

With first-class skills and rich experience, Creative Biolabs offers services for generation and validation of chimeric T cell receptor (chTCR), which is an attractive strategy to genetically modify and redirect the specificity of T cells in adoptive immunotherapy.

Chimeric T cell receptors (chTCR)

Figure, Chimeric T cell receptor. A, Strategies for chTCR; B, A typical chimeric receptor.

Genetically-modified T lymphocytes expressing T cell receptors (chTCR) specific for tumor cells have been widely investigated for cancer therapy. chTCR is an approach that uses the gene encoding modified TCR or monoclonal antibody chains to endow the TCR with high affinity to tumor associated antigens (TAAs). Typically, chTCR consists of three functional regions: extracellular domains, transmembrane domains and intracellular signaling domains. The extracellular fragments made from TCR or tumor-specific antibody are designed to recognize and bind target cells such as cancer cells. As shown in the figure A, the TCR can be conventional or a single chain and the specific antibody can be Fab or single-chain variable fragment (scFv). ScFv is used more frequently than Fab in recent researches. Transmembrane domain is important to overcome the mispairing of chTCR with endogenous TCR chains. To proliferate and respond on an antigen, T cells relies on the co-stimulatory signals. Accordingly, the transmembrane and intracellular signaling domains may be derived from primary activation molecules, co-stimulatory molecules and intracellular protein kinases, such as CD3ζ or FcεRI. A hinge is constructed for linking the extracellular fragments and signaling domains. Additionally, the modification of primary human T cells from healthy donors could be used to generate humanized chTCR (hchTCR) specific for adoptive T cell immunotherapy for cancers. As the chTCR is not restricted by MHC molecules which natural TCR depends on the generated supernatural T cells can be an ideal tool in cancer therapy.

Creative Biolabs have professional experts from different disciplines to ensure the construction of robust and reliable chimeric receptors targeting your concerned antigens.

Regerences:

  1. Andreas Hombach, et al. T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends Mol Med. 2010 Feb; 16(2):77-87.
  2. Kershaw MH, et al. Supernatural T cells: genetic modification of T cells for cancer therapy. Nat rev Immunol. 2005 Dec; 5 (12): 928-40.
  3. Dong Wang, et al. Construction and expression of humanized chimeric T cell receptor specific for chronic myeloid leukemia cells. Biotechnol Lett. 2012 Jul; 34(7):1193-201.


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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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