A Mathematical Model of TCR-T Cell Therapy for Cervical Cancer.

Autor: Wang Z; Department of Mathematics, University of Maryland, College Park, MD, 20742, USA., Cho H; School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ, 85281, USA., Choyke P; Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Levy D; Department of Mathematics, University of Maryland, College Park, MD, 20742, USA. dlevy@umd.edu., Sato N; Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. saton@mail.nih.gov.
Jazyk: angličtina
Zdroj: Bulletin of mathematical biology [Bull Math Biol] 2024 Apr 16; Vol. 86 (5), pp. 57. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1007/s11538-024-01261-9
Abstrakt: Engineered T cell receptor (TCR)-expressing T (TCR-T) cells are intended to drive strong anti-tumor responses upon recognition of the specific cancer antigen, resulting in rapid expansion in the number of TCR-T cells and enhanced cytotoxic functions, causing cancer cell death. However, although TCR-T cell therapy against cancers has shown promising results, it remains difficult to predict which patients will benefit from such therapy. We develop a mathematical model to identify mechanisms associated with an insufficient response in a mouse cancer model. We consider a dynamical system that follows the population of cancer cells, effector TCR-T cells, regulatory T cells (Tregs), and "non-cancer-killing" TCR-T cells. We demonstrate that the majority of TCR-T cells within the tumor are "non-cancer-killing" TCR-T cells, such as exhausted cells, which contribute little or no direct cytotoxicity in the tumor microenvironment (TME). We also establish two important factors influencing tumor regression: the reversal of the immunosuppressive TME following depletion of Tregs, and the increased number of effector TCR-T cells with antitumor activity. Using mathematical modeling, we show that certain parameters, such as increasing the cytotoxicity of effector TCR-T cells and modifying the number of TCR-T cells, play important roles in determining outcomes.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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