The key difference between chimeric and humanized antibody is that chimeric antibody is an antibody made up of domains of different species, and it carries a larger stretch of non-human protein while humanized antibody is an antibody made up from modified protein sequences of non-human species.
Chimeric and humanized antibodies are two types of non-human antibodies. They are developed as therapeutic antibodies in the laboratories. When comparing humanized antibodies and chimeric antibodies, humanized antibodies carry a lower risk of immunogenicity than chimeric antibodies. In chimeric antibodies, mouse constant regions have been replaced by human constant regions. In humanized antibodies, mouse amino acids in the complementarity-determining regions (CDRs) are transferred into the human V-framework regions.
CONTENTS
1. Overview and Key Difference
2. What is a Chimeric Antibody
3. What is a Humanized Antibody
4. Similarities Between Chimeric and Humanized Antibody
5. Side by Side Comparison – Chimeric vs Humanized Antibody in Tabular Form
6. Summary
What is a Chimeric Antibody?
Chimeric antibody is a non-human antibody which is made up of domains from different species. For example, the Fc region of a mouse mAb can be replaced by those regions of human antibody or any other species antibody. Chimeric antibodies having human constant domains and mouse variable domains are cheaper than humanized antibodies.
Figure 01: Chimeric and Humanized Antibodies
Chimeric antibodies retain the original antibody’s antigen specificity and affinity. Hence, they are valuable tools for in vitro and in vivo research and diagnostic assay development. Infliximab, rituximab and abciximab are several examples of chimeric antibodies. Infliximab or Remicade is used to treat rheumatoid arthritis. Rituximab or Rituxan is used to treat cancer.
What is a Humanized Antibody?
Humanization is a critical step in producing therapeutic antibodies from non-human sources. This process involves the transfer or grafting of critical non-human amino acids onto a human antibody framework. Primarily, the mouse amino acids in the complementarity-determining regions (CDRs) are transferred into the human V-framework regions. The resultant antibody is called a humanized antibody. When producing, human content is introduced as much as possible in order to reduce the risk of immunogenicity. But it also introduces enough non-human content in order to maintain the original binding activity of the parent antibody. Therefore, humanized antibodies are partly mouse Ig and partly human Ig.
Humanized monoclonal antibodies are used to treat a variety of conditions, including cancer. Humanization of antibody greatly reduces the immunogenic potential in vivo compared to chimeric antibodies. Trastuzumab (Herceptin) is the first humanized antibody developed for the treatment of breast cancer.
What are the Similarities Between Chimeric and Humanized Antibody?
- Chimeric and humanized antibodies are non-human antibodies.
- They are from non-human sources.
- Both have protein sequences made more similar to human antibodies.
- They are monoclonal antibodies produced mainly by mice or rodents.
- They are therapeutic antibodies.
- Moreover, they are used to treat a variety of conditions, including cancers.
- These antibodies can be used as controls for preclinical lead identification and potency assays for the development of novel therapeutics.
What is the Difference Between Chimeric and Humanized Antibody?
Chimeric antibody is an antibody which has its original antigen-binding variable domains with the constant domains from a different species. Humanized antibody, on the other hand, is an antibody from non-human species whose protein sequences are modified to increase their similarity to antibody variants produced naturally in humans. So, this is the key difference between chimeric and humanized antibody.
Moreover, the chimeric antibody carries a larger stretch of non-human proteins while humanized antibody does not carry a larger stretch of non-human proteins.
Below inforgrphic shows more differences between chimeric and humanized antibody.
Summary – Chimeric vs Humanized Antibody
The use of antibodies, especially monoclonal antibodies, as therapeutics has a long history. Chimeric and humanized antibodies are therapeutic monoclonal antibodies derived from non-human sources. Chimeric antibodies are developed by replacing the murine constant regions by human constant regions. Humanized antibodies are developed by introducing the mouse complementarity-determining regions (CDRs) into the human V-framework regions. Thus, this is the key difference between chimeric and humanized antibody. When compared to humanized antibody, chimeric antibody has a larger stretch of non-human protein.
Reference:
1. Almagro, Juan C., et al. “Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy.” Frontiers, Frontiers, 24 Nov. 2017, Available here.
Image Courtesy:
1. “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