VIB-RUG Department of Molecular Biomedical Research

Molecular ImmunoBiotechnology Unit

 

 

 

 

 

 

 

 

Antibodies are attractive tools to develop therapeutics.

Here's why:

bullet

one can select a specificity to a target of choice, and the antibody will preferentially bind to these cells. In principle, any target exposed to the extracellular environment will work. 

bullet

human antibodies can now be made to human target molecules: by protein engineering, by selection from synthetic libraries, or by immunization of transgenic mice carrying human antibody genes.

bullet

by selecting the right target molecule,

bullet

antibodies can transfer a signal to the cell,

bullet

or can block a receptor for its ligand,

bullet

or it can alarm the immune system by opsonizing the cell, resulting in complement activation or Fc-mediated neutrophile binding.

bullet

one can couple extra functions to the antibody, which are then preferentially targeted to a specified cell. Examples of such extra functions are:

bullet

a toxin to kill the cell

bullet

a radioactive compound to sterilize a certain body region

bullet

an enzyme to convert a harmless prodrug to a toxic compound, only at the site of the target cell.

bullet

a signaling molecule such as a cytokine, to locally activate the immune system and mark the target cell as "dangerous"

bullet

a bispecific reagent, to crosslink immune effector cells to the target cells and activate the immune system to clear up the target cell, with a possible effect of vaccination and extra protection.

bullet

Using recombinant DNA expression techniques, new antibody molecules can be made, using domains from the parent antibody molecule, with altered properties:

bullet

smaller molecules have a better capacity to penetrate into the tissue

bullet

complete antibody molecules have a very long serum persistence, 
bullet

small molecules (<60-80 kDa) are filtered very rapidly through the kidney 

bullet

Complete antibodies are protected from metabolism by Fc-tail  binding to the FcRn receptor

bullet

Glycosylation on complete antibodies also prolongs serum persistence

 

A long serum persistence is a favorable feature when the antibody has a passive function, e.g. capturing a target molecule. However, when the molecule has some toxicity or carries out some activity a long serum persistence is often not wanted. Instead, it would be more preferred to reach a favorable blood/target ratio in a short time. Smaller antibody fragments lacking the Fc-tail have these properties. But when the molecules become too small, they are rapidly removed by kidney filtration, with a half life of about 30 minutes. This results in a poor binding of the reagent to the target cells: simply because the contact time is just too short!

 

An ideal molecule would have the best of both worlds: good tissue penetration, and a body persistence that is long enough to allow sufficient accumulation at the target site.
Not so long ago, a general disbelieve was notable that antibodies would ever meet the "magic bullet" promise scientist had been talking about for almost a century. Now, antibodies are successfully used in the clinic. Examples are Herceptin® and Rituxan®, for use in cancer therapy (breast cancer and lymphoma resp.).

See here other monoclonals introduced in the clinic.

A large amount of antibodies are now in clinical trails by NIH. In the near future, a major part of FDA licensed biologicals will involve antibodies.

 

ARPBU Up Abs_table

[Antibodies] [Immunotherapy] [BsAb] [Tribody]

 

Home

Contact

Research projects

Publications

After eight

Check out 

links to:

MABs on the market
Antibody Companies
Immune Therapy Companies
Custom protein expression and purification
Biotech in Flanders
Flanders Universities
Flanders Biotech Policy

                  

© 2002 Webmaster