Although generally effective, the cancer drug rituximab does not work for everyone. However, a new study finds that adding a specific human antibody to the medication might restore its cancer-killing capabilities.
Rituximab, which is sometimes sold under the brand name Rituxan, is used to treat certain autoimmune diseases and some types of cancer.
Rituximab is not a chemotherapy drug, but rather a monoclonal antibody therapy that can be used either alone or alongside chemotherapy. This type of intervention uses antibodies, which bind to specific cells or proteins, thereby stimulating the patient's immune system to attack them.
Specifically, rituximab is an antibody against a protein called CD20, which occurs most commonly on the surface of immune B cells. Rituximab is useful in treating non-Hodgkin lymphoma and chronic lymphocytic leukemia; in these conditions, the cancer primarily affects the immune cells.
Rtuximab is thought to work by using a number of mechanisms - for example, once the drug has bound to CD20, it forms a cap on one side of the cell, which draws proteins over to that side. When natural killer cells (a type of white blood cell) bind to the cap, they are more successful at triggering cell death, or apoptosis.
In short, rituximab helps the immune system to target and kill cancer cells more effectively.
The problem with rituximab resistance
When rituximab was approved for medical use in 1997, it was well received. Some researchers have referred to it as the "most substantial advancement in the treatment of B cell malignancies, since the advent of combination chemotherapy."
However, there is no such thing as a perfect drug, and rituximab does not work for everyone. In some people, it does not activate cell death. It is thought that in some of these individuals, a molecule called regulator soluble complement factor H (CFH) protects the cells from apoptosis.
A group of researchers from the Duke Cancer Institute in Durham, NC, recently investigated this mechanism in more detail; they wanted to understand whether or not they could influence this counterproductive protective mechanism to improve the effectiveness of rituximab for more people. Their results are published this week in the journal PLOS One.
The team was led by senior author Dr. Edward F. Patz, Jr., the James and Alice Chen Professor of Radiology at Duke. In earlier studies, Dr. Patz and his colleagues identified some patients who had antibodies to CFH, and who therefore had a natural ability to fight cancer.
By producing this antibody, they were able to shut off CFH, effectively removing the cancer cell's security system and leaving it open to the immune system or drugs such as rituximab.
Additional antibodies improve treatment
In the most recent set of experiments, Dr. Patz set out to understand whether the antibody to CFH could make rituximab effective in patients who were naturally resistant to it.
To begin, the researchers tested the leukemic cells of 11 patients in order to ascertain whether or not they were resistant to rituximab. Ten out of the 11 participants' tumor cells were unresponsive to the drug.
When the researchers added CFH antibody to rituximab, five of the 11 patients (45 percent) demonstrated a significant increase in the death of cancer cells.
As Dr. Patz explains, "This is a combination approach, and it appears to strip away immune protection of cancer cells. Patients who had been rituximab resistant became rituximab sensitive."
The team already have a phase 1 clinical trial planned in order to put the antibody through its paces. This future research will measure how it works on advanced solid tumors, including breast, colon, and lung cancers.
The more advanced our understanding of cancer becomes, the more complexities we find in the disease. This makes pushing for new treatments is an increasingly convoluted task.
As the authors conclude in their paper, "It is becoming increasingly clear that tumors use multiple mechanisms to evade the immune system and are often resistant to monotherapy. A better understanding of resistance mechanisms will help optimize cancer therapy."
If the results of the current study are replicated in the phase 1 trial, the new CFH antibody treatment could further improve the efficacy of an already successful cancer treatment.