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"Anta"​, "Block"​, "Neutra"​...but Who Are They?

 

They are sometimes qualified as an antagonist, sometimes as an agonist. Sometimes named inductive, sometimes repressive, sometimes blocking, or sometimes neutralizing. But always called antibodies.

 

 Have you ever guessed what it was about?

 

 Yes, that’s them, the biologically active antibodies.

 

Depending on the nature of the antigen, a specific antibody can demonstrate different biological functions:

  • if the target is a cell surface marker for instance, the desired effect of the mAb may involve the proliferation (induction/activation effect through a signaling cascade), the inhibition, cell maturation or even the killing of the target cell. Cell depletion will then occur through the recruitment of immune mediators with the Fc portion of the mAb to trigger antibody-dependent cellular cytotoxicity (ADCC), antibody-mediated phagocytosis cytotoxicity (ADCP) or complement-dependent cytotoxicity (CDC). 
  • if the target is a soluble molecule such as plasma protein (TNF, VEGF…) or a drug, the binding may triggers a blocking effect. When bound to the mAb, these drugs are not able to interact with their normal targets anymore. Of course, blocking effect can also occurs via the cell surface receptor like the so-well known immune checkpoint inhibitors (targeting CTLA-4, LAG3, PD1 and PDL1).
  •  if the target is an infectious organism, the desired function of antibodies may be neutralization of the foreign host, so disabling the virus, bacteria or other. In fact, most licensed vaccines teach the body how to make neutralizing antibodies.

 

Unfortunately, many difficulties can appear on the way of the raise of biologically functional antibodies. We can name :

  • the epitope masking by variable loops or multimerization event,
  • the presence of cryptic binding domains,
  • the very high binding affinity of the target for its receptor, which makes the generation of inhibitory antibodies extremely challenging,
  • the very narrow window for neutralizing antibodies to act before the establishment of virus infection and its genome integration into cell host.

Either from a classical hybridoma approach or by phage display technique, 

we have over the years learned to tackle all these obstacles to offer you the best possible references.