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Generation of large numbers of functional NK cells without feeders or serum

2022· article· en· W4313407023 on OpenAlexaff
Tim Le Fevre, Elaine Ang, Albertus W. Wognum, Stephen J. Szilvassy, Allen Eaves, Sharon A. Louis, Nooshin Tabatabaei-Zavareh

Bibliographic record

VenueThe Journal of Immunology · 2022
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsTerry Fox Research InstituteStemcell Technologies
Fundersnot available
KeywordsIonomycinK562 cellsCD16BiologyInterleukin 21Interleukin 12Flow cytometryCD49bJanus kinase 3Lymphokine-activated killer cellCD69ImmunologyNatural killer cellInnate immune systemNK-92Cell biologyMolecular biologyCytotoxic T cellCD3Immune systemIL-2 receptorCD8T cellIntracellularIn vitroBiochemistry

Abstract

fetched live from OpenAlex

Abstract Natural killer (NK) cells are innate lymphocytes that modulate immune responses by secreting proinflammatory cytokines, and provide antitumor and antivirus activity. The ability to generate therapeutically relevant numbers of functional NK cells is critical for the development of advanced cellular immunotherapies. We have developed a streamlined culture workflow that enables expansion of functional NK cells without using either feeder cells or serum. Fresh human NK cells were isolated from peripheral blood using EasySep™, then cultured in ImmunoCult™ NK Cell Expansion Medium in plates coated with ImmunoCult™ NK Cell Expansion Coating Material. NK cells were fed, harvested, and replated on days 7 and 10 – 11 prior to phenotyping and functional assessment on day 14. The average frequency of CD56+ CD3− NK cells was 88% (range 75 – 96%, n=34), 74% (range 49 – 92%) of which expressed CD16, with an average expansion of 88 fold (range 3 – 454). Expanded NK cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, or co-cultured with K562 cells. As detected by intracellular flow cytometry, the average frequency of interferon-γ+ among NK cells was 68% (range 41 – 90%, n=7) and 43% (range 12 – 55%) when stimulated by PMA/ionomycin or K562 cells, respectively. Similarly, the frequency of degranulated NK cells (CD107a+) was 81% (range 35 – 97%, n=7) and 64% (range 35 – 97%), respectively. The ability of expanded NK cells to kill target K562 cells was visualized by activated caspase in co-cultures with labeled K562 cells using the Incucyte® imaging system. At an effector:target ratio of 1:1, an average of 50% of K562 cells were killed (range 45 – 56, n=3). These results show large numbers of functional NK cells can be generated.

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)0.001
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 score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.003

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 head0.027
GPT teacher head0.250
Teacher spread0.223 · 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

Citations0
Published2022
Admission routes1
Has abstractyes

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