We recently did an antibodies for dummies post. You might well ask why “monoclonal” antibodies gets its own dummy feature write up. That would be like asking why antibiotics are so special. The discovery of monoclonal antibodies in 1975 might be the most underrated and largely unknown scientific discoveries of the 20th century. Monoclonal antibodies not only revolutionized treatment for Blood Cancer and other cancers, but for dozens of other maladies as well. In theory a monoclonal antibody can be designed to treat most any illness known to man. What about coronavirus? Yes, that too. Monoclonal antibodies are in development to treat COVID19 and might yet be the treatment that saves the world.

So what are monoclonal antibodies? As with most all questions involving medicine and disease, we have to start with cell biology. Since this is a blood cancer page, lets start with blood cells. We have different types of blood cells, white blood cells among them. White blood cells are a critical part of our immune system. Lymphocytes are a type of white blood cell. B-cells are a type of lymphocyte. B-cells are our cells that create antibodies. Several types of blood cancer (including CLL and most lymphoma) is a cancer of our B-cells.

Antibodies are a Y shaped protein that can bind to pathogens like viruses and bacteria. Should you inhale a COVID19 virus particle, your B-cells will recognize it as an invader. Over time your B-cell will analyze the virus and create super specific antibodies that will latch on (bind) to that virus and nothing else, and then kill the virus by a variety of methods.

The idea for monoclonal antibodies dates back to before 1900 when a German physician named Paul Ehrlich proposed the idea of “magic bullets”, antibodies one might create in a lab to target certain pathogens. It was a brilliant idea, but science was not far advanced enough to test his theory. Imagine all the discoveries Galileo might have made had he had a computer and an electron microscope.

Fast forward to 1975 when a pair of researchers, César Milstein and Georges Köhler, developed a technique for creating cells that could create streams of identical antibodies. Their invention built on years of scientific research on the immune system and cell culture (growing cells outside the body). It worked by merging two kinds of cells—cancerous human B cells and spleen cells from mice that had been induced to produce a specific antibody.

Thinking through the names of things helps. Mono mean one. A clone is any cell or individual which is identical to another. Anyone remember Dolly the sheep? Monoclonal antibodies are a clone of identical antibodies designed to target a specific molecule on the surface of a cell.

Antibodies grown from mice are murine (of mice) antibodies. This is where thinking through the names gets fun. Who knows what a Chimera is? In Greek mythology, Chimera a fire-breathing female monster with a lion’s head, a goat’s body, and a serpent’s tail. A chimeric monoclonal antibody is one that is part mouse, part human. Now we even have fully humanized monoclonal antibodies as well. Did you know that just knowing the name of a monoclonal antibody tells you what type it is and what it treats?

Lets use rituximab as an example. Rituximab is a CD 20 monoclonal antibody used to treat cll. It is the “R” in FCR, a combination drug therapy for CLL commonly thought of as a chemotherapy option. [It also appears in other chemotherapy combinations such as R-CHOP used for lymphoma.] Rituximab is not a chemo drug though. It is a monoclonal antibody, a “mab”. Almost All monoclonal antibody drugs have names that end in “mab”. What about Gazyva, you say? Gazyva is just a brand name for obinutuzumab, as is Rituxin for rituximab or Advil for ibuprofen.

B-cells express a molecule on their surface known as CD 20, among many other molecules. Rituximab is an antibody that binds to CD 20 and puts in motion a process that allows cell death. Rituximab can kill our healthy B-cells too, but not to worry, our body will make more healthy B-cells with the hope the cancerous ones will not come back as quickly. Scientists can create monoclonal antibodies for just about anything.

There is more to their name than just the “mab” suffix. The “xi” in rituximab is a substem that tells us it is a chimeric monoclonal antibody. The “tu” tells us it acts on a tumor, with cll our cll cells can be considered a tumor, just not a solid tumor. How about obinutuzumab? Well its a mab because it ends in mab. And it has a substem “tu” in it so it acts on a tumor. Instead of the “xi” substem, it has a “zu” as one of its substems. All “mabs” with “zu” in the name are humanized monoclonal antibodies.

The naming system works the same way with monoclonal antibodies that treat other illnesses. Abciximab (Reopro) is a blood thinner. The “xi” tells us its a chimeric antibody, part human part animal. The “ci” substem tells us it impacts the cardiovascular system. Monoclonal antibodies that treat cancers typically have a “tu” in their name, indicating they act on a tumor.

Human cells function in very complex ways. They sometimes need to communicate with other cells to do their job and they can have all sorts of molecules on their surface. These molecules are involved with how cells interact and play a role in how they live and die. Cells that have more of a certain molecule than they are supposed to have are said to “overexpress” that molecule. CLL cells overexpress CD 5, indeed our doctors use a process called flow cytometry to diagnosis our cll by looking for CD 5 and other molecules on the surface of our cells.

All of these molecules are potential “targets” for monoclonal antibodies, hence the term “targeted therapy”. Proteins that are located on the surface of the B cells in CLL cells and can be potential targets by antibodies include CD20, CD 40, HLA-DQ, CD 72, CD27, CD45, CD70, CD5, HLS-DR, CD52, Ig, CD21, CD19, CD120b, HLA-DP, CD37, MHC-class I, and CD19. Alemtuzumab (Campath) is a monoclonal antibody that targets CD52. As you read this piece, scientists could be designing new and exciting monoclonal antibodies that target any of the molecules listed above. The more options we have, the better.

So hopefully now you have at least some idea of what you doctor is offering you if he/she prescribes you a monoclonal antibody. If you want to show off, ask him if the one picked for you is humanized or chimeric and what molecule he is targeting. Just kidding, no one likes a show off.

And while designing these drugs is in the realm of brilliant scenarists, the concept of a magic bullet antibody drug is quite simple. It is to create and mass produce a specific antibody to bind to a cell or pathogen. I do think it but a matter of time before they develop a magic bullet monoclonal antibody for COVID19. Time is a relative term, but they have been making “mabs” for almost fifty years now, so you can bet they are all over it.

I suppose the most surprising thing to me about monoclonal antbodies and all the illnesses they treat, is how such an amazing and life changing discovery still files under the radar. It seems to me the potential benefits for monoclonal antibodies far exceeds that of antibiotics, which are limited to bacterial infections.

Blood Cancer for Dummies

• Introducing Blood Cancer for dummies
• Cell biology and blood cancer for dummies
• Fish testing and chromosomes for dummies
• Mutated and unmutated CLL for dummies
• Viruses for dummies – blood vancer / corona edition
• Covid for dummies – part deux
• Ibrutinib and BTK inhibitors for dummies
• Antibodies (immunoglobulins) for dummies
• Monoclonal antibodies for dummies
• Clonal evolution for dummies