As a leading custom service provider, Creative Biolabs has been devoted to the development of T cell therapy for many years, such as T cell receptor (TCR) gene therapy. By altering the specificity of T cell receptor (TCR), we can genetically modify T cells to enhance their tumor-killing activity, which is an attractive approach. Creative Biolabs offers product and services for TCR-modified T cells.
There are clinical researches that have shown the feasibility and clinical potential of TCR-modified T cells as treatments for cancers. The first clinic report of such therapies is about melanoma. In this case, a TIL was isolated from a resected melanoma lesion and the TCR against the melanoma antigen recognized by T cells (MART1) was cloned and transducer T cells. Now there have been several published reports of positive clinical responses to T-cell therapies.
In order to alter T-cell specificity, genetically modified TCR therapies are developed. They are achieved by the expression of specific TCR α and β chains to mediate the antigen-recognition process. Generally, to construct modified TCR, genes that encode the α- and β-chains of TCR are identified and isolated from the T cells of the rare patients who respond to tumors and then transduce T cells or their precursors to create tumor antigen-specific T cells. During the process to generate a successful tumor antigen-specific TCR, the first important issue is to identify an appropriate target sequence, which can be from tumor-reactive T cells or generated anti-tumor T-cell antigens. There are two approaches to generate highly active anti-tumor T-cell antigens. The first method is to use human tumor proteins to immunize transgenic mice which express human MHC to generate high-affinity TCR targeting these antigens. The other method is allogeneic TCR gene transfer. For this method, tumor-specific T cells are isolated form a patient having tumor remission. The TCR sequence can be used to the transducer T cells of other patients who suffer the same disease but have no response. Moreover, the TCR genes need to be humanized for the subsequent use. Based on these two approaches, in vitro technologies can be utilized to alter and optimize the TCR sequence to enhance the strength of the interaction of TCR with target antigen, increasing tumor-killing activity. The strategies that we use to improve the properties of TCR sequences include altering TCR gene structure, developing murine-human hybrid TCR and chimeric TCR.
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Michaela Sharpe and Natalie Mount. Genetically modified T cells in cancer therapy: opportunities and challenges. Dis Model Mech. 2015 Apr;8(4):337-50.
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