Modeling predicts differences in CAR T cell signaling due to biological variability
Tserunyan, V.; Finley, S. D.
Show abstract
In recent decades, chimeric antigen receptors (CARs) have been successfully used to generate engineered T cells capable of recognizing and eliminating cancer cells. The structure of CARs frequently includes costimulatory domains, which enhance the T cell response upon antigen encounter. However, it is not fully known how the CAR co-stimulatory domains influence T cell activation in the presence of biological variability. In this work, we used mathematical modeling to elucidate how the inclusion of one such co-stimulatory molecule, CD28, impacts the response of a population of engineered T cells under different sources of variability. Particularly, our simulations demonstrate that CD28-bearing CARs mediate a faster and more consistent population response under both target antigen variability and kinetic rate variability. We identify kinetic parameters that have the most impact on mediating cell activation. Finally, based on our findings, we propose that enhancing the catalytic activity of lymphocyte-specific protein tyrosine kinase (LCK) can result in drastically reduced and more consistent response times among heterogeneous CAR T cell populations.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Epigenetic Instability May Alter Cell State Transitions and Anticancer Drug Resistance 94%
- Mathematical Model of a Personalized Neoantigen Cancer Vaccine and the Human Immune System: Evaluation of Efficacy 94%
- Agent-based model predicts that layered structure and 3D movement work synergistically to reduce bacterial load in 3D in vitro models of tuberculosis granuloma 94%
Similar papers in this journal
Similar papers in this journal
- ERK activation in CAR T cells is amplified by CD28-mediated increase in CD3ζ phosphorylation 97%
- A Population Model Reveals Surprising Role of Stochastic Cell Division in Epigenetic Memory Systems 94%
- Neural tube patterning: from a minimal model for rostrocaudal patterning towards an integrated 3D model 94%
Similar papers in this journal
- Simulations probe the role of space in the interplay between drug-sensitive and drug-resistant cancer cells 93%
- The influence of circadian rhythms on CD8+ T cell proliferation upon vaccination: a mathematical modeling perspective 93%
- Interactive dynamics of matrix adhesion and reaction-diffusion predict diverse multiscale strategies of cancer cell invasion 93%
Similar papers in this journal
- Escherichia coli chemotaxis to competing stimuli in a microfluidic device with a constant gradient 91%
- Data-Driven Flow-Map Models for Data-Efficient Discovery of Dynamics and Fast Uncertainty Quantification of Biological and Biochemical Systems 90%
- Systematic sensitivity analyses of growth modelling to evaluate the robustness of Genome Scale Metabolic Network models -- case study with the filamentous fungus Penicillium rubens 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.