What Are Monoclonal Antibodies and How Do They Treat CLL?

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Topics include: Treatment and Understanding

What are monoclonal antibodies, and why are they important for CLL patients?  From MD Anderson Cancer Center, CLL experts Dr. Zeev Estrov and Dr. Michael Keating describe the function and properties of antibodies.  As Dr. Keating says, “Antibodies are key elements in everything we do in CLL, because eventually most patients will develop significantly low levels of the normal gamma globulins."

Provided by CLL Global Research Foundation, which received support from AbbVie Inc., Genentech Inc., Gilead Sciences, Janssen Pharmaceuticals, Inc., Pharmacyclics, Inc. and Teva Pharmaceuticals.

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Transcript

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Andrew Schorr:   

So first of all, Dr. Estrov, what is an antibody?  And these letters and numbers, what are we talking about?

Dr. Estrov:            

Okay.  So in simple words, cells express on the surface different proteins.  An antibody is something that the body makes that binds to this protein and affects the cell.  The protein that is expressed by the cell is an antigen.  And the protein that binds to whatever is expressed on the cell is an antibody.  Some of the antibodies we can generate them in the lab, and they destroy CLL cells.

And there are several of them, and their numbers keep increasing.  Which kind of proteins are we going to go after?  The number is increasing.  And I think that the first proof of principle came from the work of J. Levey in Stanford University who discovered that anti-CD-20 antibodies, CD-20 that expressed on the surface of several cells like lymphoma cells or CLL cells can destroy the cells. 

Let me just mention—Andrew may not like me for expanding a little bit.  When I learned—and I used to teach—CLL was the easiest disease to teach.  It’s an expansion of mature-looking lymphocytes that are not now plastic; they’re not functional.  We don’t have a treatment.  All we have is cloanbatril that will control the counts.  That’s it.

Today, 40 percent of the patients who have CLL with mutated immunoglobulin and heavy changing are cured with the FCR regimen.  So this is what Dr. Keating has developed in MD Anderson.  This is the standard of care for these patients worldwide.  And it’s a big achievement.  It’s a disease that could not be cured.  And at least for a subset of patients, CLL can be cured. 

This is a paradigm shift.  And we will keep working on it.  We will cure CLL. 

Andrew Schorr:                  

So just to help you understand a little bit, so the monoclonal antibodies, like I had rituximab (Rituxan), some other people have had it here, too, around the world.  Jeff had a different one, ofatumumab or Arzerra that’s on there.  These are like cruise missiles, homing in, as he said, on some signal, some little antenna on the surface of the cell.  So the cruise missile says: oh, there’s the signal; boom, trying to kill the cell.  Now the problem is, it can kill healthy cells, right, Dr. Keating?  So it’s pretty selective but not totally selective.  But adding that to FC made a huge difference.

Dr. Keating:         

I think one of the things we have to realize is that some of you around here are receiving gamma globulin replacement IVIG.  And that’s because your natural antibody level is low.  So every time we get attacked by a virus or a bacteria or a fungus, we make these antibodies.  And as Dr. Estrov said, the antibodies attach to an antigen.  So the viruses and bacteria have different antigens in human cells.  So you make an antibody against them, and they attach to the virus. And they attach to the bacteria, and they help the body kill them.  And they’re little Y-shaped things with a couple of attachment molecules.

The way that these antibodies were developed was they took leukemic cells and lymphoma cells and injected them into rats and mice, and found out that some of the rats and mice would make antibodies which would attack leukemic human cells and human lymphoma cells.  And that led to the development of the drug.  So that all of these have somewhat different activities.  Rituxan and ofatumumab and inotuzumab are all different ways that we can remodel the antibodies so that they are a little more effective.  There are some problems, however, in that when we give these big molecules, they don’t get distributed evenly all around the body.

And even these days they’re given by infusion.  The Germans have figured out that you can actually give it subcutaneously, just a needle underneath the skin and run it in over a few hours with a chemical that makes it diffuse out so that you don’t have to have it intravenously.  There are ways now that you can get gamma globulin infusions instead of going into the hospital and getting IVIG, you can be taught at home that you can stick a needle in and do this and hook it up to a little bag of gamma globulin and run it in yourself and then take it out yourself.

And it had to be given once a week, but now Baxter has developed a way that you can have it done once a month rather than going in there.  So that antibodies are a key element of everything that we do in CLL, because eventually most patients with CLL will develop significantly low levels of the normal gamma globulins.  And it’s been somewhat difficult to figure out how to repair that trouble.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on March 6, 2016