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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.

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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.

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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