CARTmath

CARTmath models the dynamics of CAR-T cell immunotherapy in preclinical immunodeficient mouse systems to simulate interactions between non-solid tumors and CAR-T effector and long-term memory populations for hypothesis generation and protocol exploration.

Key Features:

• Three-population mathematical model: Describes interactions among non-solid tumor cells, CAR-T effector cells, and long-term memory CAR-T cells.
• Explicit biological processes: Captures tumor-induced immunosuppression, formation of a memory pool, and conversion of memory CAR-T cells into effectors upon tumor encounter.
• Parameter uncertainty modelling: Incorporates uncertainties representing individual donor variability and tumor-specific parameter differences.
• Parameter sensitivity: Simulations are sensitive to the differentiation rate from effector to memory CAR-T cells, cytotoxic capacity of CAR-T cells, tumor growth rates, and the extent of tumor-induced immunosuppression.
• Scenario simulation: Simulates various CAR-T cell immunotherapy scenarios documented in the literature for comparative analysis.

Scientific Applications:

• Preclinical in silico testing: Enables simulation-based exploration of CAR-T dynamics in immunodeficient mouse models to support preclinical studies.
• Prioritization for in vivo validation: Identifies promising therapy scenarios that warrant subsequent experimental investigation.
• Design and efficacy optimization: Supports evaluation and optimization of CAR-T cell design parameters and therapeutic strategies across different malignancies.

Methodology:

Uses a three-population mathematical model of non-solid tumors, CAR-T effector and long-term memory cells that explicitly models tumor-induced immunosuppression, memory-pool formation, memory-to-effector conversion, and incorporates parameter uncertainties for donor variability and tumor specificity with simulations sensitive to differentiation rate, cytotoxic capacity, tumor growth rate, and immunosuppression extent.