EHA 2019: Dr. Susan O’Brien on Frontline Therapy in CLL
Monoclonal antibodies are a type of targeted therapy for chronic lymphocytic leukemia (CLL). There are some FDA approved therapies and even more that are being studied within clinical trials. Dr. Thomas Kipps of USCD Moore Cancer Center gave a brief talk at the Patient Empowerment and Education Meeting held April 23, 2015 about how monoclonal antibodies work. They have become very important for people who have CLL and as a result of their action survival has improved.
Monoclonal antibodies are proteins found within the blood. They are typically made when we are infected with a bacteria or a virus. The antibodies bind to the bacteria and then the bacteria is targeted for immune destruction.
The ability to engineer antibodies is very critical and we now have the capacity to make and select for the right kind of antibody that binds to a given protein or a given specificity on a CLL cell. Large quantities of a single antibody can be manufactured and that’s why it’s called monoclonal antibody.
Our bodies make a hundred billion B cells every day. 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, CD23, CD27, CD45, CD22, CD70, CD5, HLS-DR, CD52, Ig, CD21, CD19, MHC-class II, CD120b, HLA-DP, CD37, MHC-class I, and CD19.
CD20 and CD52 are proteins that are targeted by manufactured monoclonal antibodies with which you may be familiar. CD52 is the target for Campath or alemtuzumab. CD20 is a very small protein on the surface of the leukemia cell. The monoclonal antibodies bind at this particular site on the cell so it’s very specific and targeted. CD20 is the target for rituximab and more recently ofatumumab and obinutuzumab have also become available. There are a few others that are in development (Ublituximab, Veltuzumab, Ocrelizumab).
Monoclonal antibodies target the leukemia cell for destruction. The antibody binds to the tumor cell and makes it more visible to the immune system. T cells and NK cells then can see that cell and say ‘Aha, I’d better destroy that cell.’ That’s how they work.
The rate of the leukemia cell destruction is important. The effect of obinutuzumab can be very striking and it appears to be very effective at recruiting T cells to destroy the tumor cells. The dramatic reductions in cell counts in a short period of time require that clinicians monitor patients closely to avoid tumor lysis syndrome. The first infusion of the antibody can be the most problematic. Now that there has been more experience with this medication, administration is performed more slowly and other medications are also administered to avoid this potentially life-threatening adverse event.
In addition to the 3 approved monoclonal antibodies currently available, there are many different targets and there are many different antibodies waiting in the wings.
Here is the video of the lecture on monoclonal antibodies from the CRC meeting in San Diego in April 2015.
Betsy Dennison, RN 11/10/15
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