Bispecific Antibody Conjugates Service

Alpha Lifetech has been committed to researching antibody customization for many years, providing customization services for bispecific antibody design, monoclonal antibodies, polyclonal antibodies, recombinant antibodies, as well as the preparation and development of various antibodies. In addition to antibody customization, we can also provide a series of bispecific antibody purification, antibody sequencing, antibody validation, antibody conjugates, and other services. And we will choose the purification method based on the specific purpose of the customer.

The immunoglobulin produced by a single B cell with high specificity for antigens is called a monoclonal antibody. After immunizing mice, the spleen cells of the mice are fused with myeloma cells from humans or mice to form hybridoma cells, which can secrete specific antibodies. However, the human body will produce an immune response to exogenous mouse proteins. People have "humanized" mouse antibodies to give them a constant human immunoglobulin region to reduce their immunogenicity. Humanized monoclonal antibodies are widely used in biomedical and clinical applications. Currently, an increasing number of monoclonal antibody conjugates are being developed for use in medical research. Bispecific antibody, also known as bifunctional antibody, refers to an artificial antibody that can specifically bind to two different antigens or two different epitopes of the same antigen simultaneously. Compared with monoclonal antibodies, bispecific antibodies have an additional specific antigen binding site, thus possessing stronger specificity and targeting ability, which can more accurately target tumor cells and reduce off target toxicity. Bispecific antibodies can simultaneously perform multiple biological functions, such as recruiting immune cells, blocking signaling pathways, and directly killing tumor cells.

introduction to Antibody conjugation

There are antigen binding sites on antibodies, and antigen and antibody undergo antibody conjugation through these binding sites. Antibody molecules are composed of heavy and light chains, and their variable regions have high specificity, responsible for binding to epitopes of antigens. Antibody conjugation is based on the structural complementarity and non covalent interactions between antigens and antibodies. The primary structure of the antigen and antibody molecules determines their structural complementarity. The epitopes on the antigen and the Complementarity Determining Region on the antibody have a matching spatial conformation and chemical composition, allowing the antigen and antibody to bind to each other. The non-covalent interactions such as electrostatic attraction, van der Waals forces, hydrogen bonding, and hydrophobic interactions enable antigens and antibodies to tightly bind together.

Fig. 1 The site-specific antibody conjugation using payloads other than synthetic cytotoxins. (Figure source: Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins - PMC (nih.gov))

Bispecific Antibody Conjugation Technology

Bispecific antibody conjugation technology is the process of chemically or biologically linking bispecific antibodies with drugs, toxins, or other active molecules to form Bispecific Antibody Drug Conjugates. This conjugate can utilize the targeting ability of bispecific antibodies to accurately deliver drugs to the lesion site, thereby improving therapeutic efficacy and reducing side effects.

Bispecific antibodies can simultaneously bind to two different antigens or epitopes, thereby increasing the recognition accuracy and binding strength of target cells. By coupling drugs with bispecific antibodies, targeted delivery of drugs can be achieved, increasing the concentration of drugs at the lesion site and enhancing therapeutic efficacy. Targeted delivery of drugs can reduce the distribution of drugs in other parts of the body, thereby reducing the toxic side effects of drugs.

The principle of chemical coupling method is to couple two complete monoclonal antibodies or Fab2 fragments into a bispecific antibody through a chemical coupling agent. Two monoclonal antibodies or Fab2 fragments bind to the target antigens A and B, respectively. Suitable chemical coupling agents are used for coupling reactions with two monoclonal antibodies or Fab2 fragments to form bispecific antibodies. The selection of chemical coupling agents is important, as their impact on antibody activity, safety, and carcinogenicity need to be considered. The coupling reaction conditions should be strictly controlled to avoid loss of antibody activity.

The double hybridoma fusion method is a method of synthesizing double hybridoma cell lines by fusing two types of hybridoma cells, and then screening stable target cell lines with two antibody functions. Two types of hybridoma cells secrete monoclonal antibodies against target antigens A and B. Cell fusion technology is used to fuse two types of hybridoma cells. The fused cells are screened to obtain a hybridoma cell line that can stably secrete bispecific antibodies. Double hybridoma cell lines were expanded and cultured to prepare bispecific antibodies. The efficiency of cell fusion should be as high as possible to increase the acquisition rate of hybridoma cell lines. In addition, due to the genetic stability of hybridoma cell lines, regular identification and preservation of cell lines are required.

Application of Bispecific Antibody Conjugation

Bispecific antibody conjugates can play an important role in tumor therapy. They can recruit T cells or natural killer cells and direct these cells towards tumor cells, enhancing their killing power against tumor cells. Meanwhile, they can also block two different signaling pathways during the pathogenesis process, affecting the growth, proliferation, and survival of tumor cells. Bispecific antibody conjugates have also been applied in the treatment of autoimmune diseases, by regulating the function of the immune system to alleviate symptoms of autoimmune diseases. In addition, bispecific antibody conjugates are also used to treat other diseases such as osteoporosis and hemophilia.

Our Advantages

We cover the upstream and downstream services of antibody production, and can provide technical services from antibody preparation, bispecific antibody purification and antibody separation and purification, antibody sequencing, antibody validation, etc, , which can be used for bispecific antibody therapy.

High Expression

High protein expression in CHO cells.
Stable Storage

>2 weeks in serum at 37 °C.
No Solubility Issue

>30 mg/ml
Stable Cell Lnes

Many stable cell lines with tumor antigens have been developed to validate many bispecific antibodies