CAR-T Cell Therapy for the Treatment of ALL: Eradication Conditions and In Silico Experimentation

• Main Authors: Paul A. Valle, Luis N. Coria, Corina Plata, Yolocuauhtli Salazar
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Hemato
• Subjects: acute lymphocytic leukaemia; cancer eradication conditions; CAR-T cell therapy; complete response; in silico; mathematical modelling
• Online Access: https://www.mdpi.com/2673-6357/2/3/28

In this paper, we explore the application of Chimeric Antigen Receptor (CAR) T cell therapy for the treatment of Acute Lymphocytic Leukaemia (ALL) by means of in silico experimentation, mathematical modelling through first-order Ordinary Differential Equations and nonlinear systems theory. By combining the latter with systems biology on cancer evolution we were able to establish a sufficient condition on the therapy dose to ensure complete response. The latter is illustrated across multiple numerical simulations when comparing three mathematically formulated administration protocols with one of a phase 1 dose-escalation trial on CAR-T cells for the treatment of ALL on children and young adults. Therefore, both our analytical and in silico results are consistent with real-life scenarios. Finally, our research indicates that tumour cells growth rate and the killing efficacy of the therapy are key factors in the designing of personalised strategies for cancer treatment.