what exactly are monoclonal antibodies, and how do they work?


what are they, the process and advantages and disadvantages?

thank you!

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Monoclonal antibodies are proteins made in laboratories that are similar to antibody proteins in our bodies, so they bind to the same receptors.

Monoclonal means that these are clones of a single antibody, as opposed to polyclonal antibodies which are made from different immune cells and bind to multiple receptors.

To say it differently, if you injected a very tiny bunny into your blood stream, your immune system would deal with it by generating thousands of antibodies to the different features of the bunny – some recognize the cottony tail, some the feet, the whiskers, the ears, or the big teeth. These are the polyclonal antibodies – they know all the different parts of the bunny, and they are a mixture of multiple, unique antibodies (hence the term ‘poly’) with a single, but complex target: a rabbit. The problem with polyclonal sets of antibodies is that they are hard to reproduce batch-to-batch. You are dependent on the animal host to recreate the set, in the same proportions, and with the same recognition sites. You can’t guarantee that in different hosts.

But really, the defining feature of a bunny is the long ears, right? That’s what makes a bun. So if you can identify and purify the *one* (mono) antibody that just recognizes the bunny ears, then you have condensed the entire set down to just the best and most accurate one. Much easier to produce and should work more consistently against its target than the set.

Both have their benefits and detriments, but generally, receiving a monoclonal antibody for a medical treatment (or using it in an experiment) means we have solid expectations for how well this will work, and how to control it. Being given a polyclonal ab translates to “we expect this to work, but we won’t be able to say why, or how, or be able to control it as well” because you don’t know which antibodies in the set are necessary or successful.

Polyclonals can be kind of a black box (not always, I’m speaking generally).

They’re antibodies, but all exactly the same (as opposed to a polyclonal mixture).

Traditionally you get a monoclonal by diluting a polyclonal B cell culture obtained from an immunized animal, to the point where you’re left with just one cell per culture vessel (microplate wells, at that scale) and then growing them out again to usable numbers. Then you do a bunch of screening experiments to find actually useful clones.

The main advantage of a monoclonal is that because it’s all the same molecule, it’s consistent in its effects. That’s important when you’re looking to use it as a drug (which are also all the same active ingredient molecule, 99.99% of the time). Having to engineer all the optimizations that go into a monoclonal, into *every clone of a polyclonal*, would be a crazy amount of work as well.

The main disadvantage is that if your monoclonal raises an immune response of its own, which they notoriously do despite our best optimization efforts, anti-drug antibodies can totally stop its intended effects. Adalimumab is a textbook case. Also, if your monoclonal is intended to combat pathogens, a rapidly mutating pathogen might escape it — as omicron-lineage SARS2 did with sotrovimab and some others.

They bind to a specific part of the target protein, called the epitope. So monoclonal antibodies are more specific than polyclonal antibodies. Polyclonal antibodies bind to multiple regions on the same protein.
The advantage are that the monoclonal antibodies are specific to a small region of the protein, and are therefore less likely to have off-target effects on other proteins compared to polyclonal antibodies.
A disadvantage is that monoclonal antibodies are less sensitive. Only one monoclonal antibody binds to one protein at a time. In contrast, multiple polyclonal antibodies can bind to the same protein.
Polyclonal antibodies are good for things like western blotting and immunostaining, where offtarget protein binding is not as much of a problem whereas monoclonal antibodies are used for in vivo drug targeting and other things that need highly specific binding with low potential for off target effects