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Record W7133092310

In Vitro Generation of Human CD4 T Lineage Cells from Stem Cells

2024· dissertation· W7133092310 on OpenAlexaff
Julius Landas

Bibliographic record

VenueTSpace · 2024
Typedissertation
Language
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsCytotoxic T cellStem cellT cellCD8Progenitor cellInterleukin 21Natural killer T cellAntigen-presenting cell
DOInot available

Abstract

fetched live from OpenAlex

T cell immunotherapies are in a rapidly evolving field that aim to provide durable and curative therapies which have found recent clinical successes in treating haematological malignancies. The scope of T cell immunotherapies continues to expand to other indications, but current standards are limited by the dependency on autologous cell sources for T cell manufacturing. In vitro T cell differentiation takes various stem cell sources and converts them into large numbers of differentiated T cells. This technology has the potential to provide a readily available and sustainable source of cell material compared to autologous sources. Our current capabilities using the OP9-Delta-like 4 (DL4) cell co-culture system, a 2-dimensional monolayer culture, produces the early gamut of T cell progenitors as well as functionally mature cytotoxic CD8 T cells, but lacks the generation of helper CD4 T cells. The inability to generate helper CD4 T cells is a roadblock to realizing the full therapeutic potential of in vitro T cell differentiation. Here, I utilize retro- and lenti-viral expression systems to demonstrate the generation of CD4 single positive T cells in OP9-DL4 co-cultures through the overexpression of the CD4 T cell master regulator, ThPOK, encoded by the Zbtb7b gene. The results from this study provide initial support for the viability of generating human CD4 T cells using the OP9-DL4 cell system.

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 score0.004
Threshold uncertainty score0.012

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.002

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 head0.057
GPT teacher head0.392
Teacher spread0.335 · 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
Published2024
Admission routes1
Has abstractyes

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