A detailed introduction to engineered antibodies

Posted by beauty33 on December 12th, 2019

Genetically engineered antibodies, also known as recombinant antibodies, refer to antibody molecules expressed by transfecting appropriate receptor cells via recombinant DNA and protein engineering techniques to process and reprogram the genes encoding the antibodies according to different needs. Genetically engineered antibodies are general names of biopharmaceuticals prepared by high-tech biotechnology such as genetic engineering technology.

Introduction to genetically engineered antibodies

Since the antibodies prepared at present are all mouse-derived, when applied clinically, they are heterologous antigens to humans, and repeated injections can produce anti-mouse antibodies, thereby attenuating or losing the therapeutic effect and increasing the occurrence of hypersensitivity reactions. Therefore, in the early 1980s, people began to use genetic engineering to prepare antibodies and reduce the immunogenicity and function of murine antibodies. At present, a partial amino acid sequence of a human antibody is used to replace the sequence of some mouse-derived antibodies, and a genetically engineered antibody is prepared by modification, which is called a third-generation antibody.

The types of genetically engineered antibody

Genetically engineered antibodies mainly include chimeric antibodies, humanized antibodies, fully human antibodies, single chain antibodies, bispecific antibodies, etc.

1. Chimeric antibody:Chimeric antibody is the earliest genetically engineered antibody. It is a splicing of the V region gene of the murine antibody and the C region gene of the human antibody into a chimeric gene, and then inserted into the vector to transfect the antibody molecule expressed by the myeloma tissue. Because it reduces the composition of the mouse, reduces the adverse reactions caused by murine antibodies and helps to improve the efficacy.
2. Humanizedantibodies:The CDRs of a human antibody are substituted with the CDRs of a murine monoclonal antibody, and the antibody formed by this way is extremely rare source of murine, and is called a humanized antibody.
3. Fully human antibody:the mouse Ig gene is replacedby human Ig gene with knockout techniques, then immunize the mouse with Ag, and then generate a large number of fully humanized antibodies by hybridoma technology.
4. Single-chain antibody: Single-chain antibody is an antibody molecule that expresses the H region of Ig and the V region of L chain and is transfected into E. coli, also known as single chain fragment of variable region (sFv). SFv has strong penetrating power and is easy to enter into local tissues.
5. Bispecific Antibodies:Antibodies that recognize effector cells and antibodies that recognize target cells are linked together to form a bifunctional antibody is called a bispecific antibody. For example, a bispecific antibody made of an antibody recognizing a tumor antigen and an antibody (CD3 antibody or CD16 antibody) that recognizes a surface molecule of a cytotoxic immune effector cell (CTL cell, NK cell, LAK cell) is advantageous for the immune effector cell to exert anti-tumor effect.

The development of genetic engineering antibody

Intracellular antibody

Recently, the US FDA emphasized that genetically engineered antibodies currently account for approximately 30% of biological agents in clinical trials. Recombinant antibodies are becoming smaller and smaller, and might be reconstituted into multivalent molecules, or fused to other molecules such as radionuclides, toxins, enzymes, liposomes, and viruses. The advent of recombinant technology has led to innovation in screening, humanization, and antibody production, and has replaced hybridoma technology, making antibody-based drug design possible.