A systems and computational biology perspective on advancing CAR therapy

Tserunyan, Vardges; Finley, Stacey D.

doi:10.1016/j.semcancer.2023.05.009

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

2025

Publication Types

Select...

Article1

Preprint1

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

References 229 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Hybrid Chimeric Antigen Receptor (CAR) γδ T Cells for Oral Cancer Therapy: Enhanced Safety and Targeted Efficacy

Kamala,

Sivaperumal

2025

Clinical Oncology

View full text Add to dashboard Cite

Hybrid Chimeric Antigen Receptor (CAR) γδ T Cells for Oral Cancer Therapy: Enhanced Safety and Targeted Efficacy

Kamala,

Sivaperumal

2025

Clinical Oncology

View full text Add to dashboard Cite

Spatiotemporal dynamics of tumor - CAR T-cell interaction following local administration in solid cancers

Owens,

Rahman,

Bozic

2024

Preprint

View full text Add to dashboard Cite

The success of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic malignancies has generated widespread interest in translating this technology to solid cancers. However, issues like tumor infiltration, the immunosuppressive tumor microenvironment, and tumor heterogeneity limit its efficacy in the solid tumor setting. Recent experimental and clinical studies propose local administration directly into the tumor or at the tumor site to increase CAR T-cell infiltration and improve treatment outcomes. Characteristics of the types of solid tumors that may be the most receptive to this treatment approach remain unclear. In this work, we develop a spatiotemporal model for CAR T-cell treatment of solid tumors, and use numerical simulations to compare the effect of introducing CAR T cells via intratumoral injection versus intracavitary administration in diverse cancer types. We demonstrate that the model can recapitulate tumor and CAR T-cell data from imaging studies of local administration of CAR T cells in mouse models. Our results suggest that locally administered CAR T cells will be most successful against slowly proliferating, highly diffusive tumors, which have the lowest average tumor cell density. These find- ings affirm the clinical observation that CAR T cells will not perform equally across different types of solid tumors, and suggest that measuring tumor density may be helpful when considering the feasibility of CAR T-cell therapy and planning dosages for a particular patient. We additionally find that local delivery of CAR T cells can result in deep tumor responses, provided that the initial CAR T-cell dose does not contain a significant fraction of exhausted cells.

show abstract

A systems and computational biology perspective on advancing CAR therapy

Cited by 2 publications

References 229 publications

Hybrid Chimeric Antigen Receptor (CAR) γδ T Cells for Oral Cancer Therapy: Enhanced Safety and Targeted Efficacy

Hybrid Chimeric Antigen Receptor (CAR) γδ T Cells for Oral Cancer Therapy: Enhanced Safety and Targeted Efficacy

Spatiotemporal dynamics of tumor - CAR T-cell interaction following local administration in solid cancers

Contact Info

Product

Resources

About