Creative Biolabs is a forward-looking CRO company as well as a leading custom service provider in the field of TAC technology. By designing a novel alternative receptor, we can stimulate the nature TCR activation pathway and induce a more stable and controllable immune response. Our novel T cell antigen connector (TAC) engineered T cells can attack cancer cells effectively with strong identification capabilities, as well as low toxicity in the clinic. A wide menu of TAC-engineered T-cell therapy programs can be tailored to suit particular needs at every stage of your projects.
TAC, a T cell antigen connector, is an alternative receptor designed to redirect T cells in a TCR-dependent, MHC-independent manner. Our TAC construct has a modular design consisting of three components, an antigen-binding region, a TCR-CD3 complex region, as well as a TCR-recruitment region.
Nowadays, we offer two strategies to design and develop the TAC antigen-binding region: one would include various antibody types, such as a single-chain variable fragment (scFv), a fragment antigen-binding (Fab fragment), a diabody, or a nanobody. Another one is based on the custom sequences provided by our clients, including but not limited to, sequences derived from peptide aptamer, philomel, knottin, ankyrin repeat polypeptide, and centering. For the TCR-CD3 complex region, we usually use the protein associated with the TCR complex as the TCR binding target, like a CD3 protein, a CD3γ protein, or a CD3ε protein. For instance, several CD3 monoclonal antibodies, like clone UCHT-1, SK7, YTH 12.5, and L2K, have been widely used for binding with the TCR-CD3 complex. Furthermore, TCR co-receptor recruitment region is designed by using CD4 cytosolic and transmembrane domain or CD8 cytosolic and transmembrane domain.
Fig.1 The structure Illustration of T Cell Antigen Connector (TAC).
In addition, a panel of TAC optimization assays has been established for enhancing the safety and efficacy of TAC receptors. Our optimization strategy is mainly through the optimization of various TAC design components and the TAC production process. In recent studies, optimizing the sequence of leader signal peptides, different linkers or connectors, as well as CD3 recruitment region has shown promising data in improving the binding affinity and TAC surface expression. Meanwhile, a comparative study on the construction of TAC-T cells using different viral vectors showed that retroviruses and lentiviruses are the most suitable vectors for TAC-T delivery.
Using our proprietary platform technology, a robust TAC-engineered T cell therapy (TAC-T) pipeline has been successfully developed for the treatment of cancer types. Our lead TAC-T drug candidates TAC-001 (anti-BCMA scFv OKT3 CD4 CD3ε) and TAC-002 (anti-CD19 scFv huUCHTl CD8 CD3ε) are in development for the treatment of patients with hematologic malignancies. More design and data information can be found below.
Fig.2 B-Cell Maturation Antigen (BCMA)-Specific TAC Construct Design.
Fig.3 Flow Cytometry Analysis of BCMA TAC Expression in Human T Cells.
Fig.4 Anti-BCMA TAC T Cells Have Potential Therapeutic Activity in Multiple Myeloma.
At the moment, more than 1000 TAC constructs have been identified by our labs, each takes a different approach to activate and expand T cells against a target antigen. More breakthroughs are expected in the coming years as our researchers continue to seek alternative strategies to improve this innovative technology.
Creative Biolabs offers a series of TAC design & optimization services that are part of our integrated portfolio of TAC-engineered T-cell therapy development services. With experienced teams of scientists, researchers, and technicians, we provide a fast turnaround, and high-quality data at competitive prices for worldwide customers. Our clients have direct access to our staff and prompt feedback on their inquiries. If you are interested in our services, please contact us for more details.
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