Speaker: Philipp Altrock, Ph.D.

Assistant Member, Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute


Title: Modeling eco-evolutionary interactions between engineered and wildtype T cells to quantify therapeutic success of anti-CD19 CAR T cell therapy


Abstract: Recent clinical advances have led to multiple new cancer immunotherapies, for example second generation Chimeric Antigen Receptor (CAR) T cell therapy that target CD19+ lymphoma (B) cells. This therapy for refractory aggressive Non-Hodgkin Lymphoma (NHL) relies on expansion of engineered T-cells in order to kill targeted lymphoma cells. We explore a mechanistic modeling approach to gain quantitative understanding of the T and B cell population dynamics after CAR T cell infusion. We combine dynamical systems and statistical mechanics approaches with statistical data-analysis based on clinical data, to recapitulate CAR T cell and tumor cell densities over time. Our approach is based on the assumptions that CAR T cells compete with wild-type T cells, and that there is a feedback of antigen CD19 that is present on tumor cells onto the CAR T cell population. We predict possible patient scenarios in a stochastic framework, such as probability and expected time of cure or progression. The model can thus be leveraged to examine how additional, currently not used changes of clinical protocols, or adjustments of the cellular immunotherapy drug, can be used to further improve the current long-term complete response rate of 40%. The framework also points to unique future challenges in modeling the kinetics and dynamics of cellular immunotherapies.