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TCRm Antibody Yeast Display Development Service
TekBiotech is committed to providing customers with high-affinity and high-specificity TCRm antibody drug early discovery technology services, and providing strong support for downstream research and development work such as new antibody development, antibody humanization, TCR-T lead sequence design, antibody-drug conjugate (ADC) development, and bispecific antibody development for subsequent targeted tumor treatment.
█ TCRm Antibody Development Services Based On Yeast Surface Display Technology Background
Currently, antibody drugs for tumor treatment are mainly developed for macromolecular proteins that are markers on the surface of tumor cells, such as PD1 antibodies. There is a class of short peptides inside tumor cells, which are specific markers of the tumor, and the short peptides can be presented to the cell surface by MHC-I and MHC-II to form a super complex of histocompatibility complex-peptide (MHC-peptide). This super complex can be recognized by TCR receptors, causing cellular immune responses and killing diseased cells. In TCR recognition of MHC-peptide complex, it is similar to the process of antibody recognition of antigen, so it is potentially feasible to develop antibodies with similar functions to TCR, namely TCR analog antibodies (TCRm), and through subsequent simple modifications, such as connecting CD3 antibodies, it can effectively activate host immune cells and kill tumor cells. As shown in Figure 1, TCR is a heterodimer composed of two chains, alpha and beta, and each subunit contains a V region (variable region) and a C region (constant region), similar to traditional IgG antibodies.
Figure 1 TCR structure
MHC-peptide complex (MHC-Peptide complex) refers to a super complex formed by the tissue compatibility complex MHC and peptide. MHC is divided into MHC-I and MHC-II, as shown in Figure 2. Currently, the preclinical research is all MHC-I to form pMHC target antigens.
Figure 2 MHC structure diagram and classification
█ TCRm Antibody Development Service
Compared with traditional therapeutic antibodies, TCRm development is more difficult, mainly because the super complex formed by MHC and peptide exists in a non-covalent bond, so it is difficult to prepare a complex of the two to form a stable conformation. With reference to a large amount of literature and TCRm antibody development experience, combined with its own yeast surface display technology platform, Tek Biotech has designed and synthesized a synthetic TCRm antibody yeast surface display library with a certain MHC bias, which can quickly develop antibodies for specific types of MHC-peptide complexes for customers.
Table 1 Information table of pMHC scFv yeast display prefabricated library
MHC Type | Library Type | Screening Type | Amino Acid Mutation | Library Capacity | Antibody Form |
HLA-A-A*02:01 | Yeast display library | FACS | 9 | 10^9 | scFv |
HLA-A-A*03:01 | Yeast display library | FACS | 10 | 10^9 | scFv |
HLA-A-A*11:01 | Yeast display library | FACS | 10 | 10^9 | scFv |
As shown in Table 1, TekBiotech has developed a pre-made TCRm antibody display library based on pMHC displayed on the yeast surface, which can quickly provide customers with TCRm antibody screening services. When customers choose pre-made library screening, they only need to provide pMHC complexes or synthetic peptide information, and TekBiotech can prepare pMHC tetramer complexes for customers and conduct subsequent screening.
In addition to the above services, TekBiotech can also provide a completely de novo TCRm nanoantibody development service (see: Nanoantibody Yeast Display Service for specific processes), through the preparation of fusion "peptide-b2m-heavy chain" target antigens, from animal immunization to the final acquisition of pMHC-specific TCRm antibody development.
Further services include but are not limited to in vitro recombinant expression, affinity verification and other downstream verification experiments, antibody humanization, TCR-T lead sequence design and cell killing verification and other one-stop technical services. Customers only need to provide specific project requirements and antigen peptide-MHC complex information. TekBiotech scientists can design reasonable solutions and customize them according to customer needs to help customers develop tumor-targeted drug antibodies.
█ Service Advantages
High-quality QC quality control standards | Flexible and changeable screening strategies | Short screening cycle for prefabricated libraries | Traceable experimental records |
TCRm Antibody Yeast Display Development Service utilizes yeast display technology to screen for antibodies that specifically target the T cell receptor (TCR). In this process, the TCRm antibody gene is cloned into a yeast expression system and displayed on the surface of yeast cells.TCRm antibodies are antibodies specific to the TCR molecule, which can be used as a therapeutic or diagnostic response against TCR-mediated immunity. The advantage of yeast display technology is that it can efficiently display a large and diverse library of antibodies on the surface of yeast cells, from which antibodies with strong affinity for specific TCR molecules can be selected by high-throughput screening methods such as flow cytometry. During the screening process, the target TCRs were selected by binding to the antibodies on the yeast surface, and those with strong affinity and high specificity were selected. After several rounds of screening and optimization, highly efficient antibodies against specific TCRs can finally be obtained, providing an important tool for immunotherapy, vaccine development and other fields.
The TCRm antibody yeast display development service has many unique advantages. First, yeast display technology enables efficient cell surface antibody display, allowing each yeast cell to display a specific antibody molecule, which makes the antibody screening process highly flexible and versatile. Second, yeast, as a eukaryotic system, is able to provide correct antibody folding and post-modification, especially in terms of glycosylation, etc., which can be closer to the natural state in human immune response. This feature is crucial for the functionality of TCRm antibodies, which typically require high-affinity binding to complex TCR molecules. Third, yeast display technology has high-throughput screening capabilities, which can rapidly screen antibodies with high affinity and specificity for specific TCRs, saving a great deal of time and cost. Finally, the yeast display platform is easy to operate, low cost, suitable for large-scale antibody development and optimization, and can provide efficient development solutions for the clinical application of TCRm antibodies.
The TCRm antibody screening and optimization process is an efficient and delicate step. First, target TCR molecules provided by the customer are constructed into a diverse antibody library by combining them with nanobodies or antibody fragments. Then, these antibody genes are cloned into a yeast expression system so that each yeast cell surface displays an antibody molecule. The screening process is carried out by methods such as flow cytometry, from which those yeast cells that bind to the target TCR molecules are screened. As the number of screenings increases, the affinity and specificity of the antibody can be progressively improved. In this process, common optimization tools include the use of directed evolution methods to enhance affinity, glycosylation modifications to improve the stability and functionality of the antibody, and antigen saturation screening to further enhance the binding ability of the antibody to the TCR. After several rounds of screening, the obtained antibodies are cloned and validated to ensure that they have high affinity, high specificity and good stability and effect in clinical applications.
TCRm antibody yeast demonstration and development services have a wide range of applications in many fields. First, in the field of immunotherapy, TCRm antibodies can be used to target specific T cell receptors, thereby enhancing the recognition and clearance of cancer cells by the immune system. By screening for antibodies that recognize specific TCR subtypes, they can be used to develop new immune checkpoint inhibitors, thereby improving the effectiveness of anti-cancer immunotherapy. Secondly, in the field of vaccine development, TCRm antibodies can be used to recognize and target TCRs of infectious pathogens, thereby facilitating the clearance response of the immune system. In addition to this, TCRm antibodies can be used as a diagnostic tool to play a role in detecting immune responses associated with TCRs, helping to recognize disease markers and make early diagnosis. In biological research, TCRm antibodies can be used to study T cell-mediated immune responses, helping to reveal the mechanisms of immune responses. Finally, TCRm antibodies can also be used in cell therapy to help recognize and inhibit abnormal T cell activity and control autoimmune diseases.
Although TCRm antibody yeast display development services have many advantages, there are some limitations. First, yeast display technology may encounter difficulties in displaying and screening larger or structurally complex antibody fragments, especially for some of the more complex TCR isoforms, whose antibody conformation and binding modes may be so complex that the yeast system may not be able to fully reproduce these complex structures and functions. Second, although the yeast display platform has high efficiency in affinity screening, for some high-affinity antibodies, the screening process may be limited by affinity maturation, especially in the process of multiple rounds of screening may require finer regulation and optimization. In addition, the yeast display platform is limited in its ability to post-modify antibodies, and although yeast is capable of some glycosylation modifications, the types and effects of modifications are more limited compared with those of mammalian cells, which may affect the functional properties of TCRm antibodies in practical applications. Finally, the diversity and size of yeast-displayed antibody libraries are limited by the transformation efficiency and surface-displaying ability of yeast cells, which may need to be optimized several times to achieve the desired screening results.
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