April 19th, 2020
I hope everyone is doing well and has had a great week! I cannot believe that it is already April 19th!! To me, March felt like it lasted years, while I feel like I just blinked and we are halfway through April! Anyhow, for this weeks blog I have decided to discuss Stelara, a type of monoclonal antibody drug approved by the FDA. Now, you are probably wondering what that is, and how I chose this topic. For the “what” I will discuss in the post below. For the “how”, I chose this topic when I was watching TV. One of the commercials was for a drug called Stelara, a commercial l have maybe seen 100 times because it always plays. I was really interested into what this drug actually was that I had seen over and over again. When I googled it, I saw that it was a monoclonal antibody drug, approved by the FDA. I decided to choose this topic because we are going to be discussing monoclonal antibodies in my Microbiology class next week and I had to read about them in my textbook.
What Are Human Monoclonal Antibodies?
First, let me explain what the heck a human monoclonal antibody is. As I learned from my microbiology textbook, monoclonal antibodies are special antibodies that are developed in a laboratory. First, scientist will immunize an animal (typically a mouse or rat) to a specific disease. Then, they will harvest the specific B-cells produced in response the the specific disease the animal was immunized against. Next, the scientist will combine these short-living B-cells with myeloma cells. Myeloma cells are plasma cells which will continuously divide (malignant/cancerous) in a media. Additionally, a salient enzyme will be removed from these myeloma cells, which will inhibit these cells to grow in the presence of a drug called aminopterin. Following, the scientist will then mix the harvested b-cells from the animal with the altered myeloma cells in a medium that contains the drug aminopterin.
By adding the drug aminopterin it ensures that only the fusion products from the b-cell and altered myeloma cells will live and continue to divide/ proliferate. The products of the fusion are called hybridoma cells. These cells have inherited critical components from both of its “parent cells”. From the b-cell, it has the ability to make the specific antibodies (in response to the antigen it was immunized for) and from the myeloma cells it has the ability to continuously divide in the media. These cells are then harvested by the scientist and used for various reasons, one being for antibody therapy to treat various diseases.
Stelara
What is Stelara?
Ustekinumab, otherwise known as Stelara, is one of the FDA approved monoclonal antibody therapy drugs. Stelara is used to treat the following: Crohn’s disease, moderate or severe psoriasis, active psoriatic arthritis, and moderately to severely active ulcerative colitis.
This drug is the only FDA approved drug that targets IL-12 and IL-23, which are two types of interleukins, which are a class of cytokines, that are released by the body’s immune system in response to pathogens. Specifically, these two cytokines are released by activated macrophages and dendritic cells. IL-12 is mainly required for antimicrobial responses to intracellular pathogens (pathogens that replicate inside cells). The specific action of IL-23 is still being explored, but it is thought to be salient in the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. So, these two cytokine are pro-inflammatory, meaning they help cause inflammatory immune system. Additionally, they are apart of the body’s innate immune system.
Specifically these cytokines bind to a specific protein (p40 protein subunit) on IL-12 and IL-23. By binding to them, this drug has inhibited their ability to activate their specific T-cells. Normally these would both activate their specific T-cells and cause them to differentiate into specific type of T-helper cells to elicit an immune response. IL-12 causes T-helper cells to differentiate into T-helper 1 and IL-23 causes T-helper cells to differentiate into T-helper 17. This action of inhibition is helpful for the diseases this drug treats. For example, both psoriasis and active psoriatic arthritis, are thought to occur due to an increase in the production of T-cells, which then cause skin cells to grow at a rapid rate. This rapid growth of the skin cells is what causes the skin plaques of psoriasis to occur. Moreover, is thought by researchers/scientists that the increase in production of both IL-12 and IL-23 lead to the GI inflammation in both Crohn’s disease and ulcerative colitis. For these reasons, the action of Stelara helps to treat these diseases by inhibiting the action of IL-12 and IL-23.
Side Effects of Stelara
Like with most drugs/treatments, there are side effects. To me, it is the most comical part of all drug commercials for drugs like Stelara. It seems like half of the commercial is spent talking about possible side-effects that could occur and the other diseases that it makes you susceptible for.
The common side-effects of Stelara include:
- nasal congestion, sore throat, and runny nose
- upper respiratory infections
- fever
- headache
- tiredness
- itching
- nausea and vomiting
- redness at the injection site
- vaginal yeast infections
- urinary tract infections
- sinus infection
- bronchitis
- diarrhea
- stomach pain
- joint pain
It is also important to note that taking this drug may lower one’s ability to fight off infections and thus increase your risk of getting infections, which may include:
- Tuberculosis (TB)
- Cancer
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
- Lung Inflammation
- Other serious infections caused by a variety of bacteria, viruses, and fungi
Taking a drug like Stelara can causes these infections due to its mechanism of action. By taking Stelara, it will inhibit part of your body’s immune system (IL-12 and IL-23). By lowering your immune system you will obviously be more likely to contract other infections, which is why these people are often considered immunocompromised and take precaution. These two cytokines are very salient in one’s ability to fight off bacteria and to suppress tumors, which is while these signs and symptoms and other infections can occur. When you lower your immune system, it will make it easier for pathogens to grow to infectious amounts. When uninhibited, IL-12 acts to help the immune system respond to intracellular bacteria and viruses, which is why one is more susceptible to contracting these types of infections when on Stelara. When uninhibited, IL-23 acts to help the immune system fight off extracellular pathogens and to help fight off self-cells that are multiplying abnormally (cancer cells).
It is for these reasons it is very salient for people taking Stelara to constantly monitor how they feel and report any changes to their physician, as some of these side-effects and risks are fatal.
Thank you for reading this weeks blog! I hope you enjoyed it as much as I did. I think monoclonal antibody drugs, like Stelara, are very interesting. It shows how far modern science has come and where it could continue to go! It makes me wonder if they could use this type of treatment for people with the coronavirus. Thank you again, and look out for next weeks blog post!

