The research and development of antibodies is the most important development of biomedical science, and it is also a concrete manifestation of the theoretical knowledge of life sciences turning into real benefits. Its clinical application has gradually expanded from the initial anti-graft rejection to major areas such as cancer, autoimmune diseases, anti-infection, cardiovascular and cerebrovascular diseases, ophthalmic drugs and biosafety prevention and control. Antagonist antibodies are antibody drugs that inhibit tumor anti-immunization by targeting immune checkpoints and are a useful tool for improving the survival rate of cancer patients in the future. Creative Biolabs helps customers improve their research and development efficiency by precisely screening antagonist antibodies.
The monitoring and control of cancerous cells is one of the functions of the immune system, but as time passes and selective pressure responds, tumor cells will defend against the immune system through various strategies, allowing them to develop uncontrolled. This process is called immune escape and generally involves the expression of surface proteins that inhibit the activity of immune cells and are called immune checkpoints. Blocking the interaction of these immune checkpoints with their T cell surface receptors can restore the threat of immune cells to tumors to some extent. The antagonist antibody developed according to this principle is an antibody drug that can be specifically connected to the immune checkpoint and inhibit its function. Currently, these antagonist antibodies have shown good efficacy, either alone or in combination with traditional therapies such as chemotherapy and radiotherapy.
Fig.1 Antagonistic Antibody.
In the human-human hybridoma technology, transgenic mice, antibody library technology, and EB virus-transformed human B lymphocyte and other fully human antibody preparation techniques, phage antibody library technology is currently the most widely used technology for antibody development. Antibody phage display (APD) is based on phage genetic engineering and repeated rounds of antigen-directed selection and phage propagation. This technology allows for the selection of virtually any specific mAb in vitro, greatly facilitating recombinant production of reagents for research and clinical diagnosis, as well as drugs for human therapeutic use. Adalimumab (Shamrock) is the first all-human monoclonal antibody approved under the technology platform, and has been ranked first in the world's best-selling drug list for several consecutive years (2012-2015).
The function and genetic analysis of the screening antibodies is also an important part of our service. After cyclic panning, the phage library was obtained by phage ELISA test, and incubated on antigen-coated plates. After washing, enzyme conjugated anti-phage antibody for major capsid proteins and chromogenic substrate specific to the selected enzyme were used to develop color. If these libraries bind to the desired antigen, the enzyme causes a color change indicating the enrichment of phage binding of the particular antigen. In that case, E. coli infected with the polyclonal phage was plated and single colony was picked and expanded for monoclonal phage production. These were tested again by phage ELISA to confirm antigen binding. The phage display vector isolated from each clone was then sequenced to determine the nucleotide sequence encoding the VL and VH of the mAb bound to the antigen.
Creative Biolabs constructed a mammalian cell display system and targeted various immunological checkpoint proteins. The Computer-aided molecular design was used to obtain an antagonist antibody library, combined with a flow-through high-throughput screening of candidate antibodies; further establishment of in vitro and in vivo evaluation model to reasonably evaluate the biological activity of candidate antibodies. If you have any questions about antibody development, you can contact us by email or send us an inquiry to find a complete solution.