Phage display technology can create thousands of antibody libraries from which the desired antibody can be matched to the antigen and pooled out. Companies like Morphosys in Germany provide these type of antibodies. The only problem is that such antibodies cannot be used in therapeutics because they lack the effector site of an antibody which is the capacity of binding to a conformational epitope such as a GPCR molecule, they cannot start a complement cascade, etc. They could only detect a linear antigen in an in vitro binding assay.

I like to know if yanyone out there agrees with me or proves me wrong.

Hello Sandy, You've almost got this right. You are correct that the phage display technology of companies like Morphosys lead to Fab fragments of antibodies, which do not contain the Fc region of an intact monoclonal antibody. But you're a little off on the definition of effector function. Fabs are perfectly fine in terms of binding to conformational epitopes, cell-surface antigens, etc.. They are usually lower in affinity than the corresponding bivalent mAb, since they can only bind in a 1:1 manner, while mAbs can bind in a multivalent fashion, leading to tighter binding. As for "effector function", this is the ability of the Fc region of mAbs, which is missing in Fab fragments, to bind to Fc receptors and thereby recruit inflammatory cells and trigger a classical immune response (including, as you mention, complement mediated responses). The solution is fairly simple; the Fab can be cloned into a mAb backbone (mouse, human, etc. depending on what species you want to do your experiements in) and, voila!, there's your effector function back.

pw_18 said:

Hello Sandy, You've almost got this right. You are correct that the phage display technology of companies like Morphosys lead to Fab fragments of antibodies, which do not contain the Fc region of an intact monoclonal antibody. But you're a little off on the definition of effector function. Fabs are perfectly fine in terms of binding to conformational epitopes, cell-surface antigens, etc.. They are usually lower in affinity than the corresponding bivalent mAb, since they can only bind in a 1:1 manner, while mAbs can bind in a multivalent fashion, leading to tighter binding. As for "effector function", this is the ability of the Fc region of mAbs, which is missing in Fab fragments, to bind to Fc receptors and thereby recruit inflammatory cells and trigger a classical immune response (including, as you mention, complement mediated responses). The solution is fairly simple; the Fab can be cloned into a mAb backbone (mouse, human, etc. depending on what species you want to do your experiements in) and, voila!, there's your effector function back.

Thank you so much pw 18 your infrmation was very helpful specially that I have found out Morphosys and its related company : Antibodies by Design have already made therapeutic antibodies anti-cancer which are released for cinical trial.

Sandy,
Glad to be of help! Another company known for making fully human Fab fragments via phage display is Dyax. PW


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Thank you so much pw 18 your infrmation was very helpful specially that I have found out Morphosys and its related company : Antibodies by Design have already made therapeutic antibodies anti-cancer which are released for cinical trial.[/quote]