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Could This New Model Predict Cytokine Release Syndrome in Immunotherapy Patients?

Immunotherapy is a rapidly evolving drug class that has drastically influenced how numerous diseases are treated over the recent years, especially cancer. While many new immunotherapies are increasing cancer survival rates, tools to predict how the immunotherapy will impact a patient’s immune system are not sufficient. In a new study, researchers have been able to develop a method to characterise the events that occur when patients with chronic lymphoid leukaemia (CLL) are given the immunotherapy rituximab to better predict potential side effects that may occur.

Rituximab is used to treat a range of diseases in which B cells are malignant, due to its ability to bind to the CD20 protein on the B cell and attract natural killer cells to destroy the B cell. While this action itself is specific and does not lead to many side effects, binding of rituximab to B cells can activate proteins in the blood that signal danger, which can ultimately cause cytokine release syndrome (CSR). Although CSR is normally mild, it can become life-threatening. The unpredictable nature of this response is a challenge to physicians, which led the researchers to develop an analysis method that provides patient-specific information on such responses.

In the study, the researchers utilised the human whole blood ‘loop’ system, using blood from healthy controls and patients with CLL. It was observed that in healthy individuals only a reduction in B cells occurred, whereas in patients with CLL, this B-cell depletion as well as CRS occurred. Current methods only capture part of the story as they are based on purified cells or serum components, but by using a whole-blood model, this new analysis takes into account all the blood-circulating immune cells, in addition to the proteins and metabolites in the blood serum.

Dr Mark Cragg, coauthor of the study, from the University of Southampton, Southampton, UK, summarised the findings: “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.” Dr Sara Mangsbo, coauthor of the study, Uppsala University, Uppsala, Sweden, added: “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.”