Chronic Lymphocytic Leukemia (CLL) is a cancer affecting B-lymphocytes, a type of white blood cell. These immune cells normally fight infections, but in CLL, they become abnormal and multiply uncontrollably. Cells have surface markers, called Cluster of Differentiation (CD) markers, which help identify them. CD20 is an important marker in CLL.
What is CD20?
CD20 (Cluster of Differentiation 20) is a protein found on the surface of B-lymphocytes. It belongs to the MS4A (membrane-spanning 4-domain family A) protein family and is present on B cells from an early pre-B-cell stage until maturity.
CD20 plays a role in the normal functioning of healthy B-cells, including their activation, proliferation, and differentiation. It is involved in regulating calcium ion conductance across the cell membrane, a process important for cell signaling. CD20 also interacts with the B-cell receptor (BCR) complex, aiding in B-cell activation and antibody production.
Why CD20 Matters in CLL
The presence of CD20 on cancerous B-lymphocytes is a defining characteristic of CLL. Detecting CD20, alongside other specific markers like CD5, CD19, and CD23, is crucial for accurately diagnosing CLL and differentiating it from other types of leukemia or lymphoma. CLL cells typically show a dim expression of CD20 compared to normal B cells.
Flow cytometry is the primary method used to identify and quantify CD20 on cells in a patient’s blood or bone marrow. This technique allows doctors to analyze thousands of cells rapidly to determine which markers are present and at what levels. The percentage of CD20-positive cells can offer insights into disease progression, acting as a prognostic indicator. For instance, a higher percentage of CD20 expression in newly diagnosed CLL patients may be associated with a better prognosis.
Targeting CD20 for Treatment
The presence of CD20 on CLL cells makes it a valuable target for cancer treatment. This approach, known as “targeted therapy,” involves using specific markers on cancer cells to selectively attack them while minimizing harm to healthy cells. Monoclonal antibodies are specifically engineered to bind to the CD20 protein on the surface of CLL cells.
Once these antibodies bind to CD20, they work through several mechanisms to destroy the cancer cells. One way is through Antibody-Dependent Cellular Cytotoxicity (ADCC), where the antibody tags the cancer cell, signaling immune cells to attack and kill it. Another mechanism is Complement-Dependent Cytotoxicity (CDC), where the antibody activates a part of the immune system called the complement system, which then directly lyses the cancer cell. Some antibodies can also induce direct cell death (DCD) in the cancer cells upon binding to CD20.
Common CD20-Targeted Therapies
Several CD20-targeted monoclonal antibody drugs are commonly used in CLL treatment. Rituximab, a chimeric (mouse-human) type I antibody, was among the first developed to target CD20 and is often integrated into CLL treatment, frequently in combination with chemotherapy. It primarily eradicates CLL cells through CDC and ADCC.
Obinutuzumab, marketed as Gazyva, is a newer humanized, glycoengineered type II anti-CD20 antibody. It exhibits a stronger ability to induce ADCC and direct cell death compared to rituximab, while having weaker CDC activity. Obinutuzumab is often used in combination with chemotherapy for previously untreated CLL patients, and has shown improved outcomes compared to rituximab-containing regimens in some studies. These therapies are typically administered intravenously, and patients may experience infusion-related reactions, especially during the first infusion, along with potential side effects like neutropenia. The specific choice of therapy depends on various factors, including the patient’s overall health, specific disease characteristics, and prior treatments.