Clinical cancer research is my area, so in sync with all of our discussion about antibodies, complement and such, this seemed like an appropriate topic. I'm not trying to be a drug rep for Genentech here; I just find such an ironic treatment for cancer pretty interesting.
Imagine you, the esteemed Inflammablog4 contributor, have been having a string of very bad luck. First, you felt a lymph node in your neck get inflamed. The node didn’t go down and you had it removed, pathology came back and said they want to see your bone marrow. You oblige, and have a bone marrow biopsy (not as painful as you thought, but still not pleasant); you also have a CT scan. Now you’re in your oncologists office, and he just dropped the ‘C’ word. Cancer.
Doc: You have cancer, more specifically, follicular CD20+ B-cell lymphoma.
You: What does that mean?
Doc: Well, you’re making to many B-Cells. They’re invading your lymph nodes, and making a mess.
You: You mean those cells that make antibodies? What’s the treatment for this?
Doc: We can treat you with antibodies.
You: Wait, what?!?!
Now, there are many types of lymphomas. Not just Hodgkins or Non-Hodgkins. There’s a monoclonal antibody (rituximab) that is used to treat many types of lymphomas (It’s also used for leukemia, rheumatoid arthritis, and many other diseases). To keep things focused, let’s just focus on follicular CD20+ B-Cell lymphoma.
The diagnosis of follicular CD20+ B-cell lymphoma can be broken down word by word. Lymphoma is a disease of lymphocytes. Follicular means that the disease involves areas of lymph nodes that are packed full of b-cells that form a round-ish area. CD20+ B-cell describes that your cancer involves b-cell lymphocytes that express the CD20 receptor.
Rituximab is an IgG monoclonal antibody (mAb) that specifically targets CD20. The IgG will bind to your CD20+ b-cells and activate complement. Bye, bye malignant b-cells. The good news: you have a targeted therapy for your cancer (along with a cyclphosphamide, vincristine, and prednisone chemotherapy regimen). The drug has been shown to improve overall progression free survival by more than double that of CVP alone (2.67 years vs. 1.25 years) (Marcus m39021 trial; The terminology used by Genentech in the later stages of this clinical trial is actually under fire by the FDA, check it out).
The bad news: pretty much all of your b-cells (malignant or not) express CD20, as do some other types of lymphocytes, so you may become immune compromised. Also, you may need to take out a second mortgage to afford it.
So, in essence, we are using the product of b-cells to kill b-cells. Interesting, no?
hey there. I am also in the cancer area, and monoclonal antibodies are also used to treat solid tumors, for example non small cell lung cancer. They can target growth factor receptors such as EGFR. An example that works for this receptor is Cetuximab.
ReplyDeleteThat is very interesting that they are using what is causing the cancer to fight the cancer, hopefully they will find a way to differentiate between the cancerous B-cells and the healthy B-cells, thus making the patient’s immune system not suppressed. According to the Mayo Clinic monoclonal antibody therapy are antibodies that are engineered to look like our antibodies but take the cancer cells and tumors so that our immune system recognizes the cancer cells easier. Part of the reason why cancer cells are able to grow without being noticed is because our immune system does not always recognize these cells as being abnormal. Cancer cells also have the growth codeon constantly on, thus the cells go out of control. The Mayo Clinic article explains what the monoclonal antibody therapy is, how it is administered, and the side effects. The monoclonal antibody therapy is administered intravenously. How often you receive the treatment depends on what kind of cancer you have and the drug you are receiving. Monoclonal antibody therapy can be used in combination with other treatments such as chemotherapy and radiation. This therapy has been approved by the FDA for the following cancers: Chronic lymphocytic leukemia, breast, colon, lung, head and neck cancers, acute myelogenous leukemia, and Non-Hodgkin’s lymphoma. The common side effects caused by the therapy include: allergic reactions, such as hives or itching, flu-like symptoms, nausea, diarrhea, and skin rashes. More serious side effects of the therapy have been reported but are rare, they include: infusion reactions which in very few cases have lead to death, dangerously low blood cell counts (including red and white blood cells, and platelets), heart problems to include heart failure and small risk of heart attack, skin problems such as sores or rashes that may lead to serious infections, and bleeding.
ReplyDeleteThe URL for the article is the following:
http://www.mayoclinic.com/health/monoclonal-antibody/CA00082
Ofatumumab (or HuMax-CD20) is another IgG monoclonal antibody that specifically targets CD20 and is also used to treat follicular lymphoma - perhaps even better than Rituximab. Rituximab is a chimeric CD20 mAb whereas HuMax-20 is a fully human mAb - although this is not the reason why HuMax-CD20 has a better efficacy.
ReplyDeleteRobin,
ReplyDeleteMy understanding is that CD20 is expressed on mature B-cells and not on any of the other immune system cell lines and yet you mentioned that CD20 is expressed by "some other types of lymphocytes". I was just wondering what other lymphocytes express CD20?
Thanks,
Kelly
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ReplyDeleteKelly,
ReplyDeleteAs a follow-up question to you, why is HuMax-20 more effective that Rituxan?
-R
Kelly,
ReplyDeleteGreat question. I should have been more clear, but I was trying to keep my post from getting too long.
There is a small subset of t cells that express CD20. There are t cell lymphomas that are CD20+ (rare). As well as other non-lymphocyte malignant cell types, such as CD20+ melanoma (also rare to have CD20+ melanocytes/melanoma stem cells).
In a phenotype study of rituximab for rheumatoid arthritis, it was found that CD20+ b and t cells were eliminated from peripheral blood by the mAb. Prior to treatment, phenotypes of CD20+ t cells were analyzed in both healthy people, and people with RA. Both groups had expression of CD20+ t cells.
http://www.ncbi.nlm.nih.gov/pubmed/19950291
I've been finding that there seems to always be an exception to the rule when it comes to immunology; which is both interesting, and frustrating!
Cheers,
-Robin
I probably should have made this addition earlier, but I just wanted to mention that NK cells (ADCC effects) also likely play a role in the destruction of CD20+ B cells treated with rituximab.
ReplyDelete