ArticleJournal of the Royal Society, Interface2021
Quantifying the limits of CAR T-cell delivery in mice and men.
Article in Journal of the Royal Society, Interface, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Predictive value of preclinical models for CAR-T cell therapy clinical trials: a systematic review and meta-analysis.Journal for immunotherapy of cancer · 2025Pooled it
- Immunotherapy for Diffuse Midline Glioma: From Preclinical Modeling to Clinical Translation.Cancers · 2026Review
- Evidence of endothelial anergy and T-cell exclusion in microsatellite stable colorectal liver metastases revealed through human hemi-liver perfusion and spatial transcriptomics.Molecular cancer · 2026Article
- Clinical pharmacology insights from recent cell and gene therapy approvals relevant to pediatrics.Pediatric research · 2026Review
- Enhancement of CD117-Targeted Bispecific T-cell Engagement by CD33-Targeted Bispecific T-cell Costimulation in Acute Myeloid Leukemia.Cancer research communications · 2026Article
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Spatio-temporal kinetics of patients' CAR-T cells in blood and serous cavity effusion: real-world clinical insights.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- PET-based tracking of CAR T cells and viral gene transfer using a cell surface reporter that binds to lanthanide complexes.Nature biomedical engineering · 2025Article
- Computational modelling of CAR T-cell therapy: from cellular kinetics to patient-level predictions.EBioMedicine · 2025Review
- Differential effects of immobilized CCL21 and ICAM1 on TILs with distinct expansion properties.Frontiers in immunology · 2025Article
- Magnetic Cellular Backpacks for Spatial Targeting, Imaging, and Immunotherapy.ACS applied bio materials · 2024Review
- Molecular mechanisms underlying the modulation of T-cell proliferation and cytotoxicity by immobilized CCL21 and ICAM1.Journal for immunotherapy of cancer · 2024Article
- Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics.NPJ systems biology and applications · 2024Article
- CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn.Nature reviews. Clinical oncology · 2024Review
- Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.Recent patents on anti-cancer drug discovery · 2024Review
- A systems and computational biology perspective on advancing CAR therapy.Seminars in cancer biology · 2023Review
- Analysis of cellular kinetic models suggest that physiologically based model parameters may be inherently, practically unidentifiable.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Cellular kinetics: A clinical and computational review of CAR-T cell pharmacology.Advanced drug delivery reviews · 2022Review
- Engineered cellular immunotherapies in cancer and beyond.Nature medicine · 2022Review
- Modeling the Potential of Treg-Based Therapies for Transplant Rejection: Effect of Dose, Timing, and Accumulation Site.Transplant international : official journal of the European Society for Organ Transplantation · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10-100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.