Uppsala University Research Points to New Method for Predicting Immunotherapy Effects

Uppsala University Research Points to New Method for Predicting Immunotherapy Effects

Uppsala University researchers in Sweden along with collaborators in the UK at University of Southampton, have produced the ability to identify differences in how the monoclonal antibody known as Rituximab interacts with the blood of healthy individuals as compared to patients with chronic lymphocytic leukemia. This leads to newfound potential to identify novel breakthroughs in immunology research and treatment.

TrialSite provides a breakdown of this interesting update.

Why is immunology so important in the field of cancer research?

Immunotherapy, novel advanced drugs and therapies that utilize the patient’s own immune system to battle tumor cells for example, is a fast growing area for exciting promise. Many new treatments help increase cancer survival rates for example.

What is Rituximab and what is it used for?

Developed by Genentech (Roche), Rituximab is a medication used to treat certain autoimmune diseases and types of cancers. A chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells, binds to this protein and triggers cell death. Approved back in 1997 first, it is now on the World Health Organization’s List of Essential Medicines. The drug’s patent expired in 2016 and a number of biosimilars have been launched. 

Challenges in some cases with use?

As discussed by Sara Mangsbo with the Department of Pharmaceutical Sciences at Uppsala University, the drug can work to help destroy malignant cells growing out of control as …[T]he monoclonal antibody binds to the CD20 protein which can help to kill the B cell” with few side effects. However…”[W]hen [Rituximab] binds to B cells it can also activate proteins in our blood that signal danger. 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.”

What did the Uppsala University investigators find in this study that can lead to breakthroughs?

While looking at differences when Rituximab monoclonal antibodies interact with the blood of healthy people and in addition patients with the disease that the monoclonal antibodies were intended to treat.  The Sweden-based team found that the immunological activation markers among the two groups differed: this could lead to new scientific breakthroughs.

Uppsala University Hospital Mattias Mattsson, out of the Hematology Clinic and co-author of the study, shared that “Immunotherapy is being used more and more frequently to treat various kinds of cancer, but we need better methods to predict the effect and risk of side effects in individual treatment recipients before the start of treatment. Analysis tools such as this potentially have great value for both the healthcare system and patients .”

What kind of  breakthroughs does this Swedish-based observation afford?

Well, for example, lead researcher Sara Mangsbo with the Department of Pharmaceutical Sciences explained “Rituximab is used to treat a range of diseases in which B cells are malignant or growing out of control. 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. The action of Rituximab is specific with few side effects, but when it binds to B cells it can also activate proteins in our blood that signal danger. 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.”

Collaboration with Britain’s University of Southampton

The Uppsala University team collaborated with Mark Cragg, co-author and professor of Experimental Cancer at the University of Southampton. Together the team studied “…how the blood loop can be used for the immune-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.”

A Breakthrough? The Blood Model

As reported by the Swedish university, this emerging tool referred to as a whole blood model refers to the ability to factor in all the immune cells circulating in the blood, as well as the myriad proteins and metabolites in the blood serum. Contributing a new dimension for the analysis of results that to date haven’t been reliably captured by known available approaches: that is those based on purified cells or serum components.

Remove the Need for Animal Studies?

This method also affords researchers the potential to investigate monoclonal antibodies without the need for animal studies. This study was based on previous studies funded by the Swedish Research Council’s financial support for 3R projects, which exist to explore replacement or reduction and/or refinement of animal studies.

Lead Research/Investigator

Sara Mangsbo, Associate Professor, Department of Pharmaceutical Sciences at Uppsala University, co-author

Mattias Mattsson, Hematology Clinic, Uppsala University, co-author

Mark Cragg, BSc, PhD, professor of Experimental Cancer at the University of Southampton, co-author

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