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TCR Affinity Optimization

Altering the specificity of T cell receptor (TCR) is one of the most popular strategies for genetically modifying T cells to enhance the tumor-killing activity of T cells. Based on the outstanding expertise and rich experience, Creative Biolabs has specially developed a novel platform for TCRs products. We will fully get involved to serve our clients if they have any requirements.

The T cell receptor (TCR), founded on the surface of T cells, is responsible for antigen recognition, consisting of the alpha (α) and beta (β) chains. Both chains have a constant region (c) and a variable region (v), and it is the variable region that determines antigen specificity. The TCR is the natural mechanism of T cells to distinguish a diseased cell from a healthy cell. All proteins are processed and presented as HLA-peptide complexes which are recognized by TCRs. T cell-based adoptive immunotherapy is a promising treatment for various types of cancer. The ability of T cells to eradicate tumor cells in patients with cancer is proved in the field of cancer therapy. However, some factors currently limit the efficacy and broad application of T cell immunotherapy, such as the mispairing between the introduced and endogenous TCR chains and it is hard to isolate T cells with adequate avidity for TAA.

Here, Creative Biolabs offer you three classics strategies to solve the problems. However, if you have other requirements, we will customize a new strategy for you.

TCR-C Murinization

The mispairing between the introduced and endogenous TCR chains can result in the acquisition of specificities that poses a significant risk for autoimmunity. Our scientists found human T cells expressing both human and mouse TCR chains preferentially express the mouse TCR chains on the cell surface in high level. Hence, Creative Biolabs will help you to modify the constant domains of the TCRα and TCRβ chains to promote the preferential pairing of the introduced TCR chains with each other by involving replacement of the C domain of human TCRα and TCRβ chains.

Incorporation of Additional Cysteine Residue

We can offer a second approach to minimize TCR chain mispairing. This method is to introduce an additional cysteine residue in both the α and β chain C domains, which increases interchain affinity by engineering a second disulfide bond into the extracellular domain of the expressed TCR. It has been proved that 95% TCR chains were properly paired when they are introduced into cysteine-modified T cells. That indicated the addition of a second cysteine bond substantially increased the propensity of the introduced TCR chains to pair with each other.

Increasing Avidity

Isolating high-avidity T cells against TAAs is frustratingly difficult, because the mature T cell repertoire consists only of those T cells with a sufficiently low avidity for self-antigens to have avoided negative selection. Creative Biolabs has developed the affinity maturation platform of phage display technology to screen mutated chains. And another strategy we can offer for increasing TCR avidity, if you want, is to modify the TCRα and TCRβ chain sequences to remove sites of N-glycosylation.

Creative Biolabs has the capability to enable you to free up your time for core work and project. Our service can be designed to meet your special needs if you have any requirements. If you are interested in our service, please contact us by E-mail and our team will get back to you as soon as possible.

TCR Affinity Optimization


  1. Thomas M, et al. T Cell Receptor Gene Therapy for Cancer. Human Gene Therapy, 2009, 20:1240–1248.

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