Toxicity Management in CAR T cell therapy for B-ALL: Mathematical modelling as a new avenue for improvement.

BioRxiv : the Preprint Server for Biology
Shalla HansonArturo Araujo

Abstract

Advances in genetic engineering have made it possible to reprogram individual immune cells to express receptors that recognise markers on tumour cell surfaces. The process of re-engineering T cell lymphocytes to express Chimeric Antigen Receptors (CARs), and then re-infusing the CAR-modified T cells into patients to treat various cancers is referred to as CAR T cell therapy. This therapy is being explored in clinical trials - most prominently for B Cell Acute Lymphoblastic Leukaemia (B-ALL), a common B cell malignancy, for which CAR T cell therapy has led to remission in up to 90% of patients. Despite this extraordinary response rate, however, potentially fatal inflammatory side effects occur in up to 10% of patients who have positive responses. Further, approximately 50% of patients who initially respond to the therapy relapse. Significant improvement is thus necessary before the therapy can be made widely available for use in the clinic. To inform future development, we develop a mathematical model to explore interactions between CAR T cells, inflammatory toxicity, and individual patients' tumour burdens in silico . This paper outlines the underlying system of coupled ordinary differential equations designed based on well-kno...Continue Reading

Related Concepts

B-Lymphocytes
Biological Markers
Burkitt Lymphoma
Malignant Neoplasms
Clinical Trials
Genetic Engineering
Inflammation
Neoplasms
T-Lymphocyte
Surface

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