New Method Predicts The Risk and Effects of Immunotherapy

Rituximab is a monoclonal antibody. Researchers have shown differences in how rituximab interacts with the blood of healthy patients compared to a patient suffering from chronic lymphocytic leukemia. This method of analysis has paved the way for important breakthroughs in immunotherapy treatment and research.

The study conducted by researchers at Uppsala University was published in the journal International Pharmacology.

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‘A new method which compares the interaction of rituximab with blood of healthy patient and a patient having chronic lymphocytic leukemia can predict the risk and effects of immunotherapy.’
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Rapid progress is being made in immunotherapy as it utilizes the body’s own immune system to fight cancer cells. Even though these treatments improve survival rate, more effective tools are required to predict how these drugs will affect an individual’s immune system.

The researchers compared the interaction of rituximab with the blood of healthy people and that of patients with a disease state. Different immunological activation markers were found between the two groups which can help in scientific breakthroughs.

Rituximab can be used to treat different diseases in which B cells (type of WBCs) are malignant or are growing out of control. It can activate proteins in the blood, which signal danger. This can lead to Cytokine Release Syndrome (CSR) characterized by mild symptoms of nausea and fever. CSR can also be life-threatening.

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Sara Mangsbo of the Department of Pharmaceutical Biosciences said, “The monoclonal antibody binds to the CD20 protein expressed on the B cell and draws natural killer (NK) cells, a part of the immune system, to the site which then help to kill the B cell. This can cause Cytokine Release Syndrome (CSR) - normally with mild symptoms in the form of nausea and fever, but it can also become life-threatening. This unpredictability is a major challenge, but the results from our study show that our analysis method can provide patient-specific information and thus become an important tool for the whole immunotherapy field if we are able to understand the individual's specific response to a given antibody-based therapy.”

To assess the toxicity, immune response, and effect of rituximab, the researchers used a complete human blood model. In the case of healthy patients, only a reduction in the number of B cells was seen, whereas in patients with chronic lymphocytic leukemia variable effects like reduction in the number of B cells and CRS were seen- except in one patient who had no NK cells.

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This study increases the understanding of what happens when rituximab comes in contact of chronic lymphoid leukemia patient blood.

As immunotherapy is used more frequently to treat different cancers, there is a need to develop different methods to predict the risk of side effects in individual treatment recipients before induction of treatment. Such tools can be useful for analysis.

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The human whole blood model considers all the immune cells circulating in the blood and the proteins and metabolites present in the blood.

Mark Cragg, co-author and Professor of Experimental Cancer Research at the University of Southampton said, “Understanding the mechanisms and resistance associated with monoclonal antibody-based drugs requires physiologically relevant tools and methods. Here, in collaboration with Uppsala University, we have studied how the blood loop can be used for the immuno-profiling of blood and drugs. The results show that there is a disease-specific immune response when blood and drugs interact. This indicates that the blood loop can be used for individual treatment and preclinical studies to identify and understand the toxicity risks for monoclonal antibody-based drug candidates.”

This method is also useful to study monoclonal antibodies without the need for animal models. Though the results are good, more extensive studies are required in specific groups of patients to help in understanding how individual immune systems react to rituximab and other monoclonal antibodies.

Sara Mangsbo said, “In the long term, we hope to take the method all the way to clinical trials as well as to the healthcare system in order to provide a better answer to which patients will respond well to specific immunotherapy treatments.”

Source-Medindia