Control-Oriented Models Inform Synthetic Biology Strategies in CAR T Cell Immunotherapy

TL;DR

An initial investigation is presented where a previously developed CAR T model is adapted for control-oriented purposes and the impact of realistic alternative activation methods as control inputs to ensure effective tumor clearance is explored.

Abstract

Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the treatment of blood cancers. Mathematical models that can predict the effectiveness of immunotherapies such as CAR T are of increasing interest due to their ability to reduce the number of experiments performed and to guide the theoretical development of new therapeutic strategies. {Following this rationale, we propose the use of control-oriented models to guide the augmentation of CAR T therapy with synthetic gene circuitry. Here we present an initial investigation where we adapt a previously developed CAR T model for control-oriented purposes. We then explore the impact of realistic alternative activation methods as control inputs to ensure effective tumor clearance.

Figures (7)

• Figure 1: Schematic of a CAR T cell recognizing a tumor cell.
• Figure 2: Interaction scheme between non-active CAR T cells $x_3$, active CAR T cells $x_2$, and tumor cells $x_1$. This scheme is adapted from barros2021cart.
• Figure 3: The modified model incorporates an additional input, denoted as $\tau$, which governs the activation of the CAR T cells.
• Figure 4: Derivation of $\dot V (x_1,z_2)$.
• Figure 5: Model results starting with arbitrary initial conditions without the control input $\tau$.