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Record W3214773827 · doi:10.3389/fimmu.2021.744763

Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience

2021· article· en· W3214773827 on OpenAlexfundno aff
Joanna Balcerek, Brian R. Shy, Amy Putnam, Lisa M. Masiello, Angela Lares, Florinna Dekovic, Luis Acevedo, Michael R. Lee, Vinh Nguyen, Weihong Liu, Sreenivasan Paruthiyil, Jingying Xu, Ashley Leinbach, Jeffrey A. Bluestone, Qizhi Tang, Jonathan H. Esensten

Bibliographic record

VenueFrontiers in Immunology · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsnot available
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesBreakthrough T1D CanadaNational Institute of Allergy and Infectious DiseasesUniversity of California, San Francisco
KeywordsMedicineManufacturing processGood manufacturing practicePolyclonal antibodiesClinical trialInternal medicineImmunologyBiologyBiotechnologyAntigenMaterials science

Abstract

fetched live from OpenAlex

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 10 6 (range 56.9-16,179 x 10 6 ). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.

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)0.027
metaresearch head score (Gemma)0.017
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.027
Threshold uncertainty score0.143

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0270.017
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.002
Science and technology studies0.0010.002
Scholarly communication0.0020.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.008
GPT teacher head0.212
Teacher spread0.204 · 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 designObservational
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

Citations29
Published2021
Admission routes1
Has abstractyes

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