Introduction to Functional Human Antibody Discovery by Premade Human Antibody Library

Antibodies have many uses in the field of biological research, such as as tools for biochemical research, disease treatment, and diagnostic tests. There are many avenues of functional antibody discovery, such as anti-peptide/protein antibodies, anti-cell-based target antibodies, bifunctional antibodies, and anti-epitope antibodies. Together, these different approaches have contributed to the development of antibodies. Based on our rich field experience and advanced research platform, Creative Biolabs provides comprehensive services to support premade antibody library screening and functional human antibody discovery.

Functional Antibody

Functional antibodies are antibodies with agonist or antagonist activity. They can effectively mimic or block physiological functions in vitro or in vivo. Being preservative-free or containing low levels of endotoxin, they have been widely used in studies such as activation, neutralization, or blockade in vivo and in vitro.

In view of the action characteristics of functional antibodies, multiple functional human antibodies against a target have become one of the most effective ways to treat certain immune responses or to fight against malignant tumors. For example, anti-CD40 antibodies are an effective biological agent for the treatment of cancer. CD40 is a type I transmembrane protein of 48 kDa in size. It is an important immune cell communication mediator, linking intrinsic and adaptive immunity. The expression of CD40 on monocytes and their progeny, macrophages, and dendritic cells, as well as on B cells, plays an important role in the performance of immune cell functions. CD40 signaling is an important trigger of the monocyte maturation process, primarily driving the differentiation of macrophages and DC cells into the M1 lineage. The binding of CD40 to the surface of DC cells promotes the production of cytokines and chemokines, induces the expression of co-stimulatory molecules, and facilitates the cross-presentation of antigens. One of the major functions of CD40L is to enhance the presentation of antigens to T cells by activating DC cells. B cells are also targets of CD40L activity. Defects in the CD40/CD40L system are associated with antibody class switching in B cells and defects in cellular hypermutation (hyper-IgM syndrome).

Since CD40 plays a key role in anti-tumor immune responses, various strategies to induce CD40 signaling have been extensively explored by research. They can be broadly categorized as agonist antibody-based approaches or CD40L-based approaches. The most important characteristic of antibodies is their high specificity for homologous epitopes. Antibodies can specifically bind to multiple unique epitopes on a given protein, including linear and conformational epitopes. Importantly, the location of the epitope plays a crucial role in activity. This was initially demonstrated by showing that antibodies with different epitopes produced different CD40 signaling cascades upon binding. The stimulatory activity of anti-human CD40 antibodies decreased as the epitope became closer to the cell membrane. Anti-CD40 antibodies typically rely on secondary cross-linking via the Fcγ receptor (FcγR) for biological activity. These Fc/FcR interactions generate other responses. For example, the Fc region mediates CDC or ADCC effects in target cells. This means that both ends of the antibody have an important role in performing their biological function. In the case of anti-CD40 antibodies, this also means that they have a mixed mode of action. This becomes particularly important when discussing therapeutic indications for anti-CD40 antibodies and comparing efficacy and safety. The lack of significant clinical activity of early anti-CD40 antibodies has prompted many improvements. Seven unique anti-CD40 antibodies are currently in clinical trials, including CP-870893, and new results have recently been published from studies focusing on new epitopes, new Fc region designs, and combination therapies to improve the limited clinical efficacy previously observed.

Creative Biolabs has a wealth of knowledge and experience in antibody phage display. We would be happy to share with you our knowledge and experience in premade phage displayed human antibody library construction and functional human antibody discovery.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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