Capturing CAR-T cell therapy dynamics through mechanistic modeling

Poster Abstract

Background and Aim

Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in treating various leukemias and lymphomas. CARs are engineered to redirect T cells to specific antigens. [1]

CAR-T PK behavior is distinct from other therapies due to its "living" nature; it is characterized by an exponential expansion, fast initial decline (contraction), and slow long-term decline (persistence). [2]

Much is still unknown about the workings of CAR-T cells in the body, and there is not a standard monitoring process. Modeling can shed light on CAR-T cell PK/PD and inform future studies.

Our aim is to reproduce typical CAR-T PK using a mechanistic modeling approach, validate our model with PD results, and understand system variability.


Our model of CAR-T cell therapy for B cell lymphoma contains the following components:

  • Bolus dose administered as part CD8+, part CD4+ drug product
  • CAR-T cells become activated when they bind to CD19 on malignant B cells
  • Activated CAR-T cells proliferate and eventually become effector cells
  • Effector cells kill B cells, which otherwise exhibit logistic growth
  • A fraction of effector cells become memory cells; the rest die
  • Model also tracks other lymphocytes which are not affected by CAR-T cells
  • Both receptors and cells are modeled explicitly
  • Receptors are synthesized and degraded

Conclusions and Future Directions

  • We were able to capture CAR-T cell PK using a mechanistic modeling approach
  • Our model can reproduce PD and provide information on characteristics of CAR-T and tumor cells that drive system dynamics

Future directions

  • More PD data will be helpful in improving model accuracy
  • The model can be used to explore and optimize properties of CAR-T cells such as expansion, CD4:CD8 ratio, and killing capacity
  • Additional model components can be included, e.g. other cell types, distribution to other tissues, and toxicity considerations


[1] Sterner, Robert C, and Rosalie M Sterner. “CAR-T cell therapy: current limitations and potential strategies.” Blood cancer journal vol. 11,4 69. 6 Apr. 2021, doi:10.1038/s41408-021-00459-7
[2] Chaudhury, Anwesha et al. “Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic-Pharmacodynamic Modeling Approaches.” Journal of clinical pharmacology vol. 60 Suppl 1 (2020): S147-S159. doi:10.1002/jcph.1691
[3] Ying, Zhitao et al. “Distribution of chimeric antigen receptor-modifed T cells against CD19 in B-cell malignancies.” BMC cancer vol. 21,1 198. 25 Feb. 2021, doi:10.1186/s12885-021-07934-1

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