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Record W4213184823 · doi:10.1016/j.omtm.2022.02.004

Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function

2022· article· en· W4213184823 on OpenAlexafffund
Sarah MacPherson, Sarah Keyes, Marisa K. Kilgour, Julian Smazynski, Vanessa Chan, Jessica Sudderth, Tim Turcotte, Adria Devlieger, Jessie Z. Yu, Kimberly S. Huggler, Jason R. Cantor, Ralph J. DeBerardinis, Christopher Siatskas, Julian J. Lum

Bibliographic record

VenueMolecular Therapy — Methods & Clinical Development · 2022
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsStemcell TechnologiesUniversity of Victoria
FundersNational Human Genome Research InstituteCanadian Institutes of Health ResearchNational Cancer InstituteNational Institutes of HealthVictoria UniversityCancer Prevention and Research Institute of Texas
KeywordsEx vivoGlutamineIn vivoPhenotypeFunction (biology)Cell biologyCell growthBiologyCellT cellCarbohydrate metabolismMetabolismCancer researchBiochemistryImmunologyImmune systemGenetics

Abstract

fetched live from OpenAlex

Ex vivo expansion conditions used to generate T cells for immunotherapy are thought to adopt metabolic phenotypes that impede therapeutic efficacy in vivo . The comparison of five different culture media used for clinical T cell expansion revealed unique optima based on different output variables, including proliferation, differentiation, function, activation, and mitochondrial phenotypes. The extent of proliferation and function depended on the culture media rather than stimulation conditions. Moreover, the expanded T cell end products adapted their metabolism when switched to a different media formulation, as shown by glucose and glutamine uptake and patterns of glucose isotope labeling. However, adoption of these metabolic phenotypes was uncoupled to T cell function. Expanded T cell products cultured in ascites from ovarian cancer patients displayed suppressed mitochondrial activity and function irrespective of the ex vivo expansion media. Thus, ex vivo T cell expansion media have profound impacts on metabolism and function.

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)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.096
GPT teacher head0.416
Teacher spread0.319 · 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 designBench or experimental
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

Citations38
Published2022
Admission routes2
Has abstractyes

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