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CD3 monoclonal antibodies: Opening a new chapter in breakthrough therapies

Introduction to CD3

Cluster of Differentiation, referred to as CD, is a very critical class of proteins or glycoproteins on the cell membrane. Among them, CD3 has a unique and important position. As a multimeric protein complex, it shoulders a heavy responsibility. In the human immune system, CD3 can be closely linked to the T cell receptor (TCR), and the two form a TCR-CD3 complex in a non-covalent manner. This complex is widely present on the surface of all mature T cells. Like a "signal soldier", it is deeply involved in the process of T cell antigen recognition, helping T cells to accurately identify foreign pathogens. At the same time, it also plays a key bridge role in the signal transduction link, which can quickly transmit external stimulation signals to the cell and trigger a series of immune response reactions. Not only that, CD3 also deeply regulates the development process of T cells, ensuring that T cells gradually grow from the initial state to fully functional immune cells, and building a strong defense line for the body to resist diseases.

CD3 Monoclonal Antibody

Monoclonal antibody (mAb) is an antibody produced by a single B cell clone that only targets a specific antigen epitope. Among the methods for preparing monoclonal antibodies, hybridoma technology is relatively mature, with less cost in the experimental process and low R&D cost, and is widely used. In 1986, the world's first therapeutic monoclonal antibody (used to prevent kidney transplant rejection) was launched. Since then, many monoclonal antibody drugs have been used to treat diseases, such as asthma. Among them, fully human antibodies have significant effects in treating diseases and have become one of the most commonly used treatments.

CD3 target protein is an important direction for the development of targeted drugs. The following is the development history of CD3 monoclonal antibodies:

In 1979, the first monoclonal mouse antibody that recognizes the CD3 surface antigen of human T cells, OKT3, appeared. In 1986, OKT3 was approved by the FDA for inhibiting rejection in solid organ transplantation. However, mouse monoclonal antibodies have high immunogenicity and great side effects. It was later discovered that the cause of the side effects was that the CD3 monoclonal antibody simultaneously bound to the Fc receptor (FcR) on the antigen presenting cell and the CD3/TCR complex on the T cell, resulting in strong activation of the T cell.

In the late 1980s, a mouse-specific anti-CD3 monoclonal antibody with few side effects was successfully developed. In the 1990s, this monoclonal antibody was used to alleviate overt diabetes NOD (non-obese diabetes, developing spontaneous autoimmune diabetes).

With the development of monoclonal technology, the emergence of chimeric antibodies has solved the immunogenicity and side effects of OKT3. Anti-CD3 recombinant antibodies are obtained by grafting the key complementary determining region for antigen recognition into the human IgG backbone to achieve humanization.

Following chimeric antibodies, humanized or fully human antibodies have gradually emerged. So far, four anti-human CD3 recombinant antibodies are in clinical development, and the immunogenicity is negligible.

CD3 Bispecific Antibodies

CD3 target protein is a good target direction in the development of bispecific antibodies. CD3 bispecific antibodies can redirect T cells to target and kill cancer cells.

Belinto is the first CD3 bispecific antibody approved for marketing. Currently, the approved CD3 bispecific antibodies are suitable for hematological tumor diseases. At present, the DLL3/CD3 bispecific antibody BI 764532 has been approved by NMPA for the treatment of frequently recurrent extensive small cell lung cancer (ES-SCLC).

TekBiotech has been committed to the field of antibodies for many years, has mature technology, and has rich experience in therapeutic antibodies. It can provide you with customized antibody drug services. In addition, TekBiotech also provides customized small molecule modification, antibody expression and purification, affinity determination, antibody sequencing, etc. to meet customer needs.

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