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

Paul Valle,Corina Plata,Luis Coria,Yolocuauhtli Salazar

doi:10.3390/hemato2030028

Abstract

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.

Highlights

Postgraduate Program in Engineering Sciences, BioMath Research Group, Tecnológico Nacional de México/IT Tijuana, Blvd
One of particular interest is that of Lee et al [11], where they performed a phase 1 dose-escalation trial on Chimeric Antigen Receptor (CAR)-T cells for the treatment of B-Acute Lymphocytic Leukaemia (ALL) on 21 patients concluding that this therapy is feasible, safe and mediates potent anti-leukaemic activity in children and young adults
In silico experimentation provides a powerful tool that could potentially be applied in the design of personalised strategies for cancer therapy administration protocols

Summary

Introduction

Postgraduate Program in Engineering Sciences, BioMath Research Group, Tecnológico Nacional de México/IT Tijuana, Blvd. Alberto Limón Padilla s/n, Tijuana 22454, Mexico; Postgraduate Program in Engineering, Tecnológico Nacional de México/IT Durango, Abstract: 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. Available treatments for ALL include, mainly, chemotherapy and stem cell transplantation

Methods

Results

Discussion

Conclusion