Difference Between Chimeric and Humanized Antibody

The main difference between chimeric and humanized antibody is that the chimeric antibody is a monoclonal antibody with a large stretch of non-human proteins whereas the humanized antibody is a non-human antibody with a protein sequence that has been modified to increase the similarity to human antibodies. Chimeric antibodies track down and illuminize the tumor regions while the antigenic region of the humanized antibodies is derived from human DNA and the variable region is derived from mouse DNA. 

Chimeric and humanized antibody are two types of monoclonal antibodies produced by mice or rodents under laboratory conditions. They are used for the administration of humans as anticancer drugs.  

Key Areas Covered 

1. What is a Chimeric Antibody
     – Definition, Structure, Function
2. What is a Humanized Antibody
     – Definition, Structure, Function
3. What are the Similarities Between Chimeric and Humanized Antibody
     – Outline of Common Features
4. What is the Difference Between Chimeric and Humanized Antibody
     – Comparison of Key Differences

Key Terms

Chimeric Antibody, Chimerization, Humanized Antibody, Humanization, Therapeutic Purposes 

What is a Chimeric Antibody 

A chimeric antibody is a combination of proteins made from human DNA and mouse DNA. Generally, two-thirds of the human DNA sequence is involved in the production of a chimeric antibody. This reduces the risk of rejection by the human immune system when administrated. Recombinant DNA technology combines the human and mouse DNA. The monoclonal antibody lines are expressed in the animal cell cultures.

Figure 1: Structure of an Antibody  

The addition of a chimeric region to these antibodies allows to track the location of the antibodies and illuminize the tumor cells in the microscopic slides. 

What is Humanized Antibody

A humanized antibody is a combination of human and mouse DNA in which human DNA is closer to 90%. The human DNA-derived proteins in the humanized antibody increase the similarity to the natural antibodies in humans to prevent rejection. During the humanization process, the created constructs are expressed in the mammalian cell cultures.

Figure 2: Monoclonal Antibodies (brown: human, blue: non-human)
top row: mouse, chimeric
bottom row: humanized, chimeric/humanized, human  

The antigenic region of the humanized antibodies is derived from human DNA. But, some of the variable regions of the humanized antibodies are derived from mouse DNA. 

Similarities Between Chimeric and Humanized Antibody 

• Chimeric and humanized antibody are monoclonal antibodies produced by lab mice or rodents. 
• They have a human DNA-derived antigenic region and a mouse- or rodent-derived variable region.  
• Chimerization and humanization are the two processes by which the mouse monoclonal antibodies are converted into a therapeutic antibody that can be used in humans. 
• Both types of antibodies are highly specific to their target. 
• They serve as anticancer drugs. 

Difference Between Chimeric and Humanized Antibody 

Definition 

Chimeric antibody refers to an antibody derived from both human and mouse DNA to which a chimeric region is also attached while humanized antibody refers to an antibody made up of a combination of human antibody and a small part of a mouse or rat antibody.  

Chimeric Region 

Chimeric Antibody has a large portion of a chimeric region while humanized antibody does not have a chimeric region. 

Amount of Human DNA  

Around 66% of human DNA is involved in the production of a chimeric antibody while around 90% of human DNA is involved in the production of humanized DNA.  

Function 

Chimeric antibody helps to track down and illuminize tumor regions while humanized antibodies are used to immunize humans. 

INN Substem 

The INN substem of the chimeric antibody is –ximab while the INN substem of humanized antibody is –zumab. 

Examples 

Some examples of chimeric antibodies are abciximab, rituximab, infliximab, and cetuximab while humanized antibodies include palivizumab, trastuzumab, bevacizumab, and natalizumab.  

Conclusion 

Chimeric antibodies have a chimeric region attached to the antibody. They have around 66% of human DNA. Humanized antibodies have around 90% similarity to the human antibody. Therefore, the main difference between chimeric antibody and humanized antibody is the structure of the antibody. 

Reference:

1. “Chimeric Antibodies.” PRRDB: PAttern-Recognition Receptor Database, Available Here
2. Harding, Fiona A, et al. “The Immunogenicity of Humanized and Fully Human Antibodies.” Advances in Pediatrics., U.S. National Library of Medicine, 2010, Available Here

Image Courtesy:

1. “Antibody chains” By Fred the OysteriThe source code of this SVG is valid. Template drawing from “The Immune System” (Public Domain) via Commons Wikimedia   
2. “Chimeric and humanized antibodies” By Antibody_je2.neutral.svg: Of this SVG version, Roland Geider (Ogre), of the original PNG version, User Je at uwo on en.wikipediaderivative work: ἀνυπόδητος (talk) – Antibody_je2.neutral.svgGeneral policies for monoclonal antibodies (PDF). World Health Organization (2009-12-18). (Public Domain) via Commons Wikimedia