Monoclonal Antibodies Made Simple

Monoclonal antibodies (-mabs) are a common source of confusion for pharmacy students. They have long, hard-to-pronounce names that all look and sound alike. It's impossible to tell them apart, let alone keep track of where they're used therapeutically.

Well that ends today, you smarty pants tl;dr pharmacy reader, you. Today we're going to show you how to make sense of the entangled maze of -mabs. We're going to show you that there is actually a system to how monoclonal antibodies are named. 

Why bother? Because you can tell most of what you need to know about a monoclonal antibody just by the name.  You can learn a few simple rules that apply everywhere instead of crowding your brain memorizing endless details that you'll eventually forget after the test.

You can perform better on tests while spending less time studying and still remember the information.

Not to mention, -mabs are the future. They aren't going anywhere. You are going to see more and more of them because they're effective (both clinically and at making money for Genzyme shareholders). 

What's in a Name?

First thing's first, all monoclonal antibodies end in -mab. You can weed out a lot of multiple choice options on a test just with that information. Go back to your immunology and remember that your antibodies are just about the most target-specific cells in your body. They ONLY bind to whatever "thing" they were designed for. This is where you've heard the phrase "lock and key."

Monoclonal antibodies behave the same way. If you make a -mab to the HER2 protein (eg. trastuzumab [Herceptin]), it will ONLY bind to the HER2 protein. This is nothing like a lot of other drugs in use. Take a drug like amitriptyline. It has activity everywhere: 5HT, NE, histamine, cholinergic, and muscarinic pathways.  

So, if you have a test question regarding "off target" side effects for a -mab, you can probably eliminate those answer choices. You aren't likely to see anticholinergic effects like dry mouth and urinary retention with -mab use, for example. 

To illustrate further, it's common knowledge that most of the "classic" chemo agents can cause bone marrow suppression and chemo-induced nausea and vomiting (CINV). However, you don't see these side effects for most -mabs used in cancer. Practically all of them are minimal emetogenic risk and it's rare to see significant effects on neutrophils or platelets.

Before the -mab

Blue = Mouse; Red = Human Image: Anypoditos, Public Domain

Blue = Mouse; Red = Human
Image: Anypoditos, Public Domain

The letter(s) that precede the -mab tell you what "source" the antibody came from. The most common sources you encounter are:

  • -o- : mouse (all mouse)
  • -xi- : chimeric (part human, part non-human)
  • -zu- : humanized (mostly human, part non-human)
  • -u- : human (all human, all the time)

How do you use this information to your advantage? Infusion reactions. While they don't have many off target effects, -mabs do cause a lot of infusion reactions. They are foreign proteins after all, and your body tends to go Wolverine berserk style when foreign proteins get into your blood.

I've conveniently listed the above sources in order of decreasing risk of infusion reaction. And that makes intuitive sense. A mouse protein would be expected to cause more of an immune response than a human protein, right?

Infusions reactions are all managed in a similar way. First, we might pre-medicate with a cocktail to reduce the risk of reaction. Editor's note: Not THAT kind of cocktail. Mai Tais have not demonstrated efficacy in mitigating the risk of infusion reactions. You'll typically see some combination of acetaminophen, an antihistamine, and/or a steroid.

It is absolutely possible to use both H1 and H2 antagonists for an antihistamine. So keep in mind that it's not out of the question to pre-medicate with both diphenhydramine and famotidine.

The other way we reduce the risk of an infusion reaction is by titrating the infusion. We start slowly. If the patient tolerates, we can increase the rate of the infusion. There are specific protocols for different -mabs, but don't worry about the details right now. Just understand the general trend. As a final point here, a patient is more likely to have a reaction the first few times receiving the infusion. The risk goes down with each dose, so the total infusion time is likely to decrease over time.

So, on a test you can now make a reasonable guess on pre-medications and administration based on the source of the -mab.

Let's take infliximab [Remicade]. You know that it's chimeric, so there's a relatively high risk of infusion reaction. If you see a test option where this is administered as a bolus or without pre-medication that choice is wrong. You can also knock out any options indicating that patients can self-administer infliximab at home--it must be administered in a health care facility.

On the other hand, adalimumab [Humira] is a fully human -mab. It is self-administered by the patient at home, without the requirement for pre-meds.

I specifically used Humira and Remicade as examples to illustrate another point. They are both -mabs for the same target (TNF-alpha). Even though they're used for similar indications, their administration is very different. This is partly because Remicade is only IV and Humira is given subcutaneously. But the main reason for that is because of the source of the antibody and the risk of infusion reactions.

Before the Source

Yep, the nomenclature goes even further. The letter or two before the source gives you a general idea of where the -mab works in the body (the target). If only all drug names were this easy, right?

Below are the common targets and nomenclature for -mabs. The letter in parentheses is optional but you may see either version in use today.

  • -c(i)- : circulatory system
  • -k(i)- : interleukin
  • -l(i)- : immune system
  • -t(u)- : tumor

This is far from an exhaustive list, but these are probably the most common you'll encounter. If you know these, you'll have a good grasp of most of the -mabs in use.

Let's apply this knowledge to help you weed out more wrong choices on a test question. If you have a scenario where a patient is going to be treated for Crohn's disease and one of the options is abciximab [ReoPro], you can remove that as an option. You know that from the prefix -ci- that abciximab is used somewhere in the circulatory system, so there's probably not much use for it in Crohn's disease. 

Similarly, you won't see basilixumab [Simulect] in the treatment of colon cancer as you know from the -li- that it works on the immune systems (specifically, it's used to prevent rejection in kidney transplants). 

Before the Target

No more! Before the target there is no set nomenclature. Drug developers are just asked to make something that "flows" nicely with the rest of the name. There's no rhyme or reason here, so you'll have to do the best you can with the above rules. 

Still, as we've demonstrated, you have a ton of information at your disposal just from the name. Use this to perform better on tests, study less, and understand more.

tl;dr Summary

  • Anything ending in -mab is a monoclonal antibody
  • The letters preceding -mab tell you the source of the antibody
  • The letters preceding the source tell you the general target of the antibody
  • Monoclonal antibodies are highly specific in binding to their target, meaning there are very few "off target" side effects
  • Monoclonal antibodies have a high rate of infusion reactions. In general, the more foreign the source of the antibody, the higher the risk of reaction

 

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