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arXiv · 2003.10236

CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models

Odelaisy Leon-Triana·Soukaina Sabir·Gabriel F. Calvo·Juan Belmonte-Beitia·Salvador Chulian·Alvaro Martinez-Rubio·Maria Rosa·Antonio Perez-Martinez·Manuel Ramirez Orellana·Victor M. Perez-Garcia
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Abstract

Immunotherapies use components of the patient immune system to selectively target cancer cells. The use of CAR T cells to treat B-cell malignancies --leukaemias and lymphomas-- is one of the most successful examples, with many patients experiencing long-lasting complete responses to this therapy. This treatment works by extracting the patient's T cells and adding them the CAR group, which enables them to recognize and target cells carrying the antigen CD19+, that is expressed in these haematological tumors. Here we put forward a mathematical model describing the time response of leukaemias to the injection of CAR T-cells. The model accounts for mature and progenitor B-cells, tumor cells, CAR T cells and side effects by incorporating the main biological processes involved. The model explains the early post-injection dynamics of the different compartments and the fact that the number of CAR T cells injected does not critically affect the treatment outcome. An explicit formula is found that provides the maximum CAR T cell expansion in-vivo and the severity of side effects. Our mathematical model captures other known features of the response to this immunotherapy. It also predicts that CD19+ tumor relapses could be the result of the competition between tumor and CAR T cells analogous to predator-prey dynamics. We discuss this fact on the light of available evidences and the possibility of controlling relapses by early re-challenging of the tumor with stored CAR T cells.

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Odelaisy Leon-Triana, Soukaina Sabir, Gabriel F. Calvo, Juan Belmonte-Beitia, Salvador Chulian, Alvaro Martinez-Rubio, Maria Rosa, Antonio Perez-Martinez, Manuel Ramirez Orellana, Victor M. Perez-Garcia. 2020-03-18. CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models. https://doi.org/10.1016/j.cnsns.2020.105570

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