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Interleukin‐12 immunotherapy in a murine model of leukemia

2008· article· en· W2289192290 on OpenAlexaff
Megan Nelles, Alain Labbe, Jagdeep S. Walia, Lintao Jia, Caren Furlonger, Takahiro Nonaka, Jeffrey A. Medin, Christopher J. Paige

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health NetworkOntario Institute for Cancer Research
Fundersnot available
KeywordsCTL*Cytotoxic T cellCD8ImmunotherapyImmunologyCancer researchSystemic administrationT cellPopulationMedicineInterleukin 2AntigenIn vivoBiologyImmune systemIn vitro

Abstract

fetched live from OpenAlex

To improve the efficacy of interleukin‐12 (IL‐12) therapy using different dosage and administration protocols than those previously used in clinic, a model of murine acute lymphoblastic leukemia (ALL) was developed employing the well‐characterized cell line 70Z/3. Administration of low dose IL‐12 by two separate methods each led to efficient tumor clearance but by way of distinct mechanisms. Direct IL‐12 administration resulted in tumor rejection by the canonical pathway, ultimately mediated by CD8 + cytotoxic T lymphocytes (CTL). However, when 70Z/3 cells themselves were transduced with a novel lentiviral vector system to express IL‐12, in vivo depletion experiments demonstrated that a CD4 + cell population alone was absolutely required for tumor rejection but not CD8 + CTLs. We also observed that the outcome of therapy is dependent more on the number and quality of cellular interactions than on the absolute amount of IL‐12 administered. An example of such a cellular interaction might be that of an IL‐12 secreting tumor cell with an antigen presenting cell, a dendritic cell or macrophage, which subsequently interacts with a CD4 + cell to induce an effector response. For this interaction to be effective, the tumor cell must produce IL‐12 above a certain threshold. Overall, our studies highlight that the method of IL‐12 administration can have a significant impact on the outcome of treatment.

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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0020.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0020.001

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 head0.052
GPT teacher head0.308
Teacher spread0.256 · 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
Published2008
Admission routes1
Has abstractyes

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