For one antigen, there are a few antibodies can bind to it according to different epitopes. When these anitbodies bind to the antigen, will it cause different cascade events? Can we predict the following cascade events based on the recognized epitopoes?
I think you're asking about in vivo immune processes. Obviously, different classes of Ab (e.g., IgM, IgA, IgG) activate different immune cascades. But in general, the same class of Ab is likely to facilitate a similar immune response, regardless the specific Ag binding site. I can think of two exceptions to this generalization.
One is that, upon binding, some Ab disrupt the physiological function of the Ag (e.g., enzyme, quaternary structure, cellular compartment). This can produce a more robust defense than non-inhibitory Ab, even though the actual immune cascade is the same.
The other is affinity/avidity. Tighter binding generally produces a more robust immune cascade. Thus many pathogen Ag are expressed with heterogeneity (e.g., E coli O & H) and/or mutate rapidly (e.g., influenza HA & NA). Such "antigenic drift" leads to poor Ab recognition and reduced immunity.
John Carter Thanks John. Let me make my question clearer. Take PD-1 mAbs for instance. There're 3 kinds of PD1 mAbs, Pembrolizumab, Nivolumab, and Cemiplimab, used in clinical cancer immunotherapy. They bind to different epitopes of PD1 and reverese the its effect on inactivating T cells. I'm wondering does it mean all mAbs of PD-1 can have the same function, no matter where they will bind to PD-1. Actually, I FEEL the answer is no. Otherwise pharmaceutical companies do not need to invistigate a ton of money to design the "special" mAb.
I'm not familiar with the specific epitopes in this Ab-Ag system. And to answer your question I probably don't need to be familiar. I suspect the epitopes are proprietary, although you may find them described in the US patent database. Are you certain they are three totally different epitopes, and not overlapping at all? Do you know whether they cross-inhibit (each other)?
It would not surprise me to learn that the epitopes overlap significantly, meaning at least two of these are "me too" drugs. Pharma spend money developing "me too" drugs because they save money compared to the first-to-market drug. The first one to market must establish clinical relevance, while "me too" can expect their drugs will work approximately as well in the clinic.
Importantly, the first one to market establishes a domain of Intellectual Property. Subsequent drugs must demonstrate a difference from the first one to earn "freedom to operate." If they function outside of that IP domain, theoretically they have a different market, even if they actually compete for the same patient population. For FTO a slightly different epitope is sufficient.
Ab binding usually inhibits the function of the Ag. Even if it doesn't inhibit the function, it usually dramatically increases catabolism/turnover of the Ag. So most mAb that bind PD1 probably inhibit PD1 function. When you make drugs out of mAb, you usually start with a dozen or so candidates and work them through the process. Many variables help determine which ones make the best drug. Binding strength and inhibitory activity are only two of those. Stability in the cell line is required, as hybridomas frequently lose chromosomes they don't need to survive. Your ability to express Ab protein at high levels in industrial cell culture to scale up for manufacture is critical. Half-life in the target organism also is important.
Note the best general strategy for any drug development from a set of lead compounds is "fail early; fail often." You push test the leads EARLY for their ability to be turned into a drug. And you eliminate the failures ASAP, so you can focus your investment on your best lead.
John Carter John, I do appreciate your valuable answer. It's pretty enlightening.
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