T cell receptor (TCR) activates T cells to enhance cellular immunity by identifying specific major histocompatibility complexes (MHC) and the presented MHC-antigen-peptide (MAP). The TCR-like antibody technology platform mainly replaces TCR with antibodies to screen out antibodies with much higher affinity and specificity than TCR, so as to effectively target intracellular antigen. Biocytogen's unique HLA/RenMab mice combined with our high-throughput antibody screening platform enable a one-step process to obtain fully human antibodies that identify MAP, ensuring a high-affinity binding in vivo while rapidly obtaining fully human antibodies.
Immunotherapy has made a great breakthrough in recent years, and antibody therapy is the core of this breakthrough. Traditional antibody therapies target cell membrane surface antigens (such as PD-1 and PD-L1) or soluble antigens. However, ideal tumor antigens (such as RAS, P53, WT1, etc.) are mainly intracellular, which is a limitation of antibody therapy, while TCR that identifies tumor antigens usually has a low affinity for the corresponding antigen, resulting in immune escape of tumor cells. The TCR-like antibody technology platform will overcome this limitation and can screen out antibodies with high affinity and specificity to identify and bind to intracellular antigens.
Intracellular antigens are degraded by proteasomes into polypeptides, some of which are identified by TAP and transferred to endoplasmic reticulum and MHC (Human MHC is known as Human Leukocyte Antigen, HLA) to form a complex (peptide-HLA) that is presented to the surface of the cell membrane; antibodies are prepared for specific peptide-HLA and targeted cell clearance is realized by identifying and binding to the intracellular specific antigen polypeptides.
Our unique HLA/RenMabTM mice express HLA based on RenMabTM mice through gene editing. This mouse model remains tolerant to HLA while producing antibodies for the specific peptide-HLA complex by antigenic stimulation, without producing antibodies for HLA. The fully human antibodies with high specificity and affinity for peptide-HLA can be obtained in a one-step process after immunization with specific antigen, combining with our high-throughput antibody screening platform (Optofluidic system, phage display, yeast display, etc.). Our TCR-like antibody technology platform combines traditional immunization methods with high-throughput antibody screening methods to efficiently obtain the fully human antibody sequences and ensure that the resulting sequences have in vivo affinity maturation.
The fully antibody sequences obtained by TCR-like antibody technology platform provide more candidates for subsequent antibody-related drugs, CAR-T, TCR-T and other fields. It provides more intracellular targets for targeted clearance of specific abnormal cells such as tumor cells, infected cells and senescent cells. In addition, TCR-like blocking antibodies can also be screened for specific cells that are attacked by the autoimmune disease, so as to avoid damage to normal tissues.