Creative BioMart is a well-known expert who is committed to developing a variety of protein therapies to improve the effectiveness and safety of protein therapy, and to allow the production of new types of proteins and effects. With years of experience, we provide customized services for T cell receptors as protein therapeutics to precisely meet customer requirements.

Introduction of Therapeutic T Cell Receptors

T cell receptors (TCRs) are proteins on the outer surface of lymphocytes that recognize and bind antigens. T cells play a key role in cell-mediated immunity, and strategies for genetically modifying T cells include chimeric antigen receptor (CAR) T cell therapy and T cell receptor (TCR) T cell therapy. Both strategies attach new receptors to the surface of cells, enabling them to attack different forms of cancer. The difference between the two is that CAR T cells bind to natural antigens on the surface of cancer cells, and TCRs are linked to major histocompatibility complex (MHC) proteins. Engineered TCR therapy equips activated T cells with specific receptors that target their complementary cancer antigens. Researchers are exploring the potential of TCRs as immunotherapeutic or immunodiagnostic reagents to specifically target pMHC complex.

Fig 1. Therapeutic T cell design: goals and strategies. (Sadelain M, et al., 2017)

Services

TCR therapy is unique in that it can identify multiple cancers that overexpress specific antigens within cells, making it more suitable for penetrating tumors. As a leading service provider of protein engineering, Creative BioMart has established a powerful T cell receptor-based protein therapeutics platform to design soluble, stable, high-affinity TCRs. In addition, we offer T cell function optimization services, including selecting good targets, finding specific TCRs, screening for the best TCR affinity, safety assessment, time and cost to achieve optimal functional capacity of engineered T cells.

Affinity and expression level of a therapeutic TCR are two key parameters that determine how much antigen is required to trigger T cell effector function. Our scientists are working to develop multiple engineering strategies to increase TCR expression levels and alter TCR affinity on the surface of T cells. Besides classic codon optimization, introduction of additional disulfide bonds between TCR chains, and introduction of murine residues into constant region domains, we also offer cutting-edge strategies for you to choose from:

• Strategies to provide additional CD3 molecules to enhance TCR expression in engineered T cells. Our gene transfer of TCR and CD3 into primary T cells enhanced TCR expression and improved recognition of antigens at low concentrations, resulting in enhanced tumor protection in vivo.
• Strategies to alter TCR affinity through T cell stimulation by low antigen concentrations. T cells with affinity-modified TCRs were efficiently stimulated by high doses of the cognate peptide but did not respond to low doses of the peptide.
• Strategies to enhance the antitumor effect of engineered T cells through the delivery of immunostimulatory cytokines. Our designed IL-12 based on cytokines-based protein therapeutics platform can effectively enhance the antitumor activity of adoptive T cell transfer.

Creative BioMart is committed to designing high-affinity TCRs that activate effector functions at low concentrations of mutant peptides. Therapeutic TCRs are powerful new drugs that greatly enhance the personalization of treatment and offer patients a higher potential for positive outcomes. We will work with you to develop the most appropriate strategy and provide the most meaningful data for your research for accelerating the research of life sciences. If you are interested in our services, please do not hesitate to contact us for more information.

References

1. Morris E C, Stauss H J. (2016) Optimizing T-cell receptor gene therapy for hematologic malignancies. Blood, The Journal of the American Society of Hematology. 127 (26): 3305-3311.
2. Sadelain M, Rivière I, Riddell S. (2017) Therapeutic T cell engineering. Nature. 545 (7655): 423-431.

• Engineering of Therapeutic Antibodies
• Engineering of Therapeutic Coagulation Factors
• Engineering of Therapeutic Cytokines and Receptors
• Engineering of Therapeutic Enzyme
• Engineering of Therapeutic Major Histocompatibility Complex Proteins
• Engineering of Therapeutic Protein Hormones
• Engineering of Therapeutic TCR-Like Antibodies