Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-$$\beta $$

Swanson, Ellen R.; Kose, Emek; Zollinger, Elizabeth; Elliott, Samantha

doi:10.1007/s11538-022-01015-5

Cited by 6 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether conjugate dynamics should be explicitly captured in mathematical models of cancer-immune interactions is incompletely understood. Mathematical modeling of biological systems provides powerful tools for formalizing and testing theories [19,20], explaining empirical observations combining mechanisms that were thought to be unrelated [21][22][23][24], and explicitly for understanding and exploring the interac-tion of the immune system and cancer [25][26][27][28]. Kuznetsov et al.…”

Section: Introductionmentioning

confidence: 99%

Integration of immune cell-target cell conjugate dynamics changes the time scale of immune control of cancer

Yang,

Traulsen,

Altrock

2024

Preprint

View full text Add to dashboard Cite

The human immune system can recognize, attack, and eliminate cancer cells, but cancers can escape this immune surveillance. The dynamics of these cancer control mechanisms by cells of the adaptive immune system can be captured by variants of ecological predator-prey models. These dynamical systems can describe the interaction of cancer cells and, e.g., effector T cells to form tumor cell-immune cell conjugates, cancer cell killing, immune cell activation, and T cell exhaustion. Target (tumor) cell-T cell conjugation is integral to the adaptive immune system’s cancer control or immunotherapy dynamics. However, it is incompletely understood whether conjugate dynamics should be explicitly included in mathematical models of cancer-immune interactions. Here, we analyze the dynamics of a cancer-effector T cell system regarding the impact of explicitly modeling the conjugate compartment to elucidate the role of cellular conjugate dynamics. We formulate a deterministic modeling framework to compare possible equilibria and their stability, such as tumor extinction, tumor-immune coexistence (tumor control), or tumor escape. We also formulate the stochastic analog of this system to analyze the impact of demographic fluctuations that arise when cell populations are small. We find that explicit consideration of a conjugate compartment can change long-term steady-state, critically change the time to reach an equilibrium, alter the probability of tumor escape, and lead to very different extinction time distributions. Thus, we demonstrate the importance of the conjugate compartment in defining tumor-effector interactions. Accounting for transitionary compartments of cellular interactions may better capture the dynamics of tumor control and progression.

show abstract

Section: Introductionmentioning

confidence: 99%

Integration of immune cell-target cell conjugate dynamics changes the time scale of immune control of cancer

Yang,

Traulsen,

Altrock

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The growing recognition of the importance of understanding the processes underpinning CSC-fueled tumor growth has led to the formulation of a number of mathematical models [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. These models offer insights into growth and differentiation rates, cell population fractions, lateral inhibition, and chemo-and radio-therapy effects, to cite a few processes.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Differentiating Therapy on Cancer-Stem-Cell-Driven Tumors

Fotinós¹,

Barberis²,

Condat³

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Other mechanisms have been explored over the past years, for example, the interactions between CAR-T, cancer and healthy cells to predict efficacy and toxicity [27,28], the efficacy of patient preconditioning lymphodepletion therapy [29], and the relation of CAR-T intracellular modulations and cellular response signaling [30]. There are also models for solid tumors [31,32,33,34] and, up-to-date, Liu et al proposed the only model that explored the interaction of activated/non-activated CAR-T and CD19+/CD19-tumor cells for patients with different therapy outcomes [35]. Reviews on modeling CAR-T cell therapy are found in [36,37,38].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Resistance to CAR-T cell Immunotherapy: Insights from a Mathematical Model

Santurio

Paixão

Barros

et al. 2023

Preprint

View full text Add to dashboard Cite

Chimeric Antigen Receptor (CAR)-T cell therapy long-term follow-up studies revealed non-durable remissions in a significant number of patients. Some of the mechanisms underlying these relapses include poor CAR T cell cytotoxicity or persistence, as well as antigen loss or lineage switching in tumor cells. In order to investigate how antigen-mediated resistance mechanisms affect therapy outcomes, we develop a mathematical model based on a set of integral-partial differential equations. Using a continuous variable to describe the level of antigen expression of tumor cells, we recapitulated important cellular mechanisms across patients with different therapeutic responses. Fitted with clinical data, the model successfully captured the dynamics of tumor and CAR-T cells for several hematological cancers. Furthermore, the role played by these mechanisms are explored with regard to different biological scenarios, such as pre-existing or acquired mutations, providing a deeper understanding of key factors underlying resistance to CAR-T cell immunotherapy.

show abstract

Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-$$\beta $$

Cited by 6 publications

References 37 publications

Integration of immune cell-target cell conjugate dynamics changes the time scale of immune control of cancer

Integration of immune cell-target cell conjugate dynamics changes the time scale of immune control of cancer

Effects of a Differentiating Therapy on Cancer-Stem-Cell-Driven Tumors

Mechanisms of Resistance to CAR-T cell Immunotherapy: Insights from a Mathematical Model

Contact Info

Product

Resources

About