CAR-T design is based on similariry of structure in Ig and TCR, simulating the variable region of TCR alpha and beta chain by single chain variable fragment (scFv) , through the identification of tumor specific antigen, directly transmitting signal to embedded artificial immune receptor tyrosine based activation sequence on a single polypeptide chain signal, and activating the intracellular Akt signaling pathway, thereby activating T cells and killing tumor cells.
CAR-T cells specifically recognize specific antigens on the surface of any tumor cell, such as proteins, carbohydrates and glycolipids, which do not require antigen processing and presentation.
After nearly more than 10 years of research and exploration, CAR-T's design has developed with several versions. The most popular recent technologies include the enhanced 4th generation CAR-T and the universal fifth generation CAR-T technology. However, most of the current clinical trials use the second generation (single costimulatory molecules) and the third generation (double costimulatory molecules) CAR-T design. The chimeric antigen receptor is composed of four parts: extracellular specific antigen recognition region, hinge region, transmembrane region and intracellular signal transduction domain. Therefore, the basic design of CAR is also a combination of these four parts optimization.
The first generation CAR-T cells fuse immunoglobulin scFv and Fc RI receptor or CD3 complex intracellular domain to form chimeric receptor; the second generation CAR-T cells add activation signals, such as CD28, OX-40 and 4-1BB on the chimeric antigen receptor, in order to improve the cytotoxicity and proliferation of T cells and prolong the survival time of T cells. Based on the understanding of the activation mechanism of T cells, CD28 molecules can provide second activation signals and further enhance the TCR/CD3 signal; the third generation CAR-T cell adds a co-activated signal on the basis of the second generation.
CAR T construction services are as follows:
Creative Biolabs team has long been engaged in the research of CAR-T, like the space structure of CAR molecules, costimulatory factor and other attributes, which can optimize the project according to the customer.
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Website: http://www.creative-biolabs.com/car-t/
