which part of an antigen should monoclonal antibodies bind to? - how to choose appropiate epitopes? (Dec/06/2008 )

Hello all,

I have to write an advisory report on the production of anti-TNFa antibodies to treat RA patients. I'm going to give advice about monoclonal antibodies, using either hybridomas or phage display libraries.

My concern is after obtaining different monoclonal antibodies , how can we choose which one is the best to pursue mass-producing (based on which criteria)? Which part of TNFa should the chosen monoclonal antibody binds to?The below is just my thinkings:

- The chosen antibody should bind to a distinct TNFa-epitope that no other proteins (e.g. TNF beta) possess. So that we ensure the antibody only works on TNFa. Is it true?

- Should that distinct epitope not be in the binding site of TNFa to TNFa receptor? So that even after TNFa molecules bind to their receptor, our antibody can still bind to them? I remember infliximab work this way.


I'd really appreciate anyone's help!!! Or at least please help me understand the criteria to choose good epitopes ^^

I am not an immunologist -- let's get that out of the way. -- but do you want to stop the TNFa from binding? If so, the epitope would need to be in the binding domain, or in such a location that the bound Ab would sterically hinder binding of TNFa to its receptor..

I agree that such an epitope should be specific to TNFa.

What about pleotropic effects? I'm sure that TNFa plays other roles in the body than just in RA. If you block them all (if that were possible), what other consequences will that have?