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Record W4310747261 · doi:10.1136/jitc-2022-005360

Computational model of CAR T-cell immunotherapy dissects and predicts leukemia patient responses at remission, resistance, and relapse

2022· article· en· W4310747261 on OpenAlexfundno aff
Lunan Liu, Chao Ma, Zhuoyu Zhang, Matthew T. Witkowski, Iannis Aifantis, Saba Ghassemi, Weiqiang Chen

Bibliographic record

VenueJournal for ImmunoTherapy of Cancer · 2022
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsnot available
FundersDivision of Chemical, Bioengineering, Environmental, and Transport SystemsYork UniversityNew York UniversityLeukemia and Lymphoma SocietyAstraZenecaNational Institute of General Medical SciencesCancer Research InstituteNational Cancer InstituteNational Institutes of HealthNational Science Foundation
KeywordsChimeric antigen receptorCD19MedicineT cellImmunotherapyClinical trialLeukemiaOncologyInternal medicineAntigenImmunologyCancerImmune system

Abstract

fetched live from OpenAlex

Abstract Adaptive CD19-targeted CAR (Chimeric Antigen Receptor) T-cell transfer has become a promising treatment for leukemia. Though patient responses vary across different clinical trials, there currently lacks reliable early diagnostic methods to predict patient responses to those novel therapies. Recently, computational models achieve to in silico depict patient responses, with prediction application being limited. We herein established a computational model of CAR T-cell therapy to recapitulate key cellular mechanisms and dynamics during treatment based on a set of clinical data from different CAR T-cell trials, and revealed critical determinants related to patient responses at remission, resistance, and relapse. Furthermore, we performed a clinical trial simulation using virtual patient cohorts generated based on real clinical patient dataset. With input of early-stage CAR T-cell dynamics, our model successfully predicted late responses of various virtual patients compared to clinical observance. In conclusion, our patient-based computational immuno-oncology model may inform clinical treatment and management.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.020
GPT teacher head0.316
Teacher spread0.296 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations41
Published2022
Admission routes1
Has abstractyes

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