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Bispecific TCRs Generation Service

Creative Biolabs provides professional bispecific TCRs design and construction services for your research. With our most devoted scientists, we are confident to deliver you an Bispecific TCR that can meet all of your required specifications.

The separation of cancer-specific T cells from patients first demonstrated a crucial role for T cells in mediating antitumor responses in vivo. TCRs expressed by CD8+ T cells specialize in binding peptides resulting from intracellular proteins and presented on the cell surface in complex with MHC molecules. T cells are ideally placed to drive an antitumor response to a great variety of targets, because most tumor antigens are of intracellular origin. However, tumors enable to and do evade T-cell attacks, usually via exploiting low-affinity antigen recognition. Compared to antibodies, the natural affinity of TCRs for their cognate antigen is weaker, commonly in the low micromolar range, and for tumor-specific TCRs antigen binding seems to be especially weak. In order to solve the inherent recognition problems of the natural T-cell repertoire, a novel technique, named immune mobilizing monoclonal T-cell receptors against cancer (Bispecific TCR) has been developed, which is depended on engineered, soluble, affinity increased monoclonal TCRs (mTCRs).

Schematic diagram of the mechanism of action of Bispecific TCRs. (Oates, J., 2013)

Figure 1. Schematic diagram of the mechanism of action of Bispecific TCRs. (Oates, J., 2013)

Bispecific TCRs

Bispecific TCR is engineered by fusing a humanized anti-CD3 single chain antibody fragment to an affinity-matured T-cell receptor that recognizes target HLA-presented peptides. As a novel class of anticancer agents, Bispecific TCR combines the power of high-affinity TCR-based antigen recognition with the immune-activating potential of the anti-CD3 antibody fragment. Technically, it overcomes the inherent recognition problems of natural T-cell to tumor cells. Furthermore, Bispecific TCR provides an opportunity to expand T cells retargeted to intracellular antigens for killing tumor cells. Altogether, these properties make Bispecific TCR to be a useful tool for cancer targeted therapy.

Mechanism of Bispecific TCRs

Several essential steps are required when a Bispecific TCR molecule works. Firstly, bispecific TCR molecules recognize and intensively bind to cancer cells exhibiting a defined target (peptide-HLA). Secondly, the free end of the Bispecific TCR molecule, refers to an anti-CD3 antibody fragment, recruits, or redirects’ circulating T cells to the tumour site. Then, the Bispecific TCR molecule generates a bridge between the T cell and the cancer cell, allowing the production of a perfectly optimised immune synapse. Finally, lytic granules are released via the re-directed and activated T cell, resulting in destruction of the cancer cell.

With our well-established bispecific TCR generation platform, the experienced scientists here at Creative Biolabs are dedicated to help you develop unique BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Oates, J.; Jakobsen, B. K. ImmTACs: Novel bi-specific agents for targeted cancer therapy. Oncoimmunology. 2013, 2(2): e22891.
2. Oates, J.; et al. ImmTACs for targeted cancer therapy: Why, what, how, and which. Molecular immunology. 2015, 67(2): 67-74.

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