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Tolerance and immunity to tumor‐associated antigen MUC1 in MUC1.Tg mice

2008· article· en· W3174824064 on OpenAlexaff
Sean O. Ryan, Michael S. Turner, Leigh Revers, Jean Gariépy, Olivera J. Finn

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsUniversity of Toronto
FundersNational Institutes of Health
KeywordsMUC1EpitopeT-cell receptorTransgeneAdoptive cell transferBiologyImmune systemAntigenImmunologyImmune toleranceGenetically modified mouseImmunotherapyT cellMolecular biologyBiochemistryGene

Abstract

fetched live from OpenAlex

Numerous adenocarcinomas aberrantly express a hypoglycosylated form of human mucin 1 (MUC1), containing epitopes with tumor‐associated mono‐ and disaccharide moieties including Tn, sialyl‐Tn, and TF antigens along with bare protein backbone. In the MUC1 transgenic mouse the immune system maintains a level of tolerance to MUC1 peptides, most notably in decreased CD4 T cell help. We are further examining the mechanisms of tolerance to MUC1 peptide (self), as compared to responses to a tumor‐associated MUC1 glycopeptide (non‐self), which should not be subject to tolerance. We have cloned a MUC1 glycopeptide‐specific MHC‐Class II restricted TCR (RFT). that is currently being used to generate TCR transgenic mice for comparative in vivo studies with MUC1 peptide‐specific TCR transgenic mice previously generated. Preliminary adoptive transfer studies have indicated that peptide‐specific TCR transgenic T cells are able to persist in both wild type and MUC1.Tg mice, but upon MUC1 immunization, only the cells in wild type recipients appear activated. Taken together our studies explore the differences in immune responsiveness to two different tumor‐associated forms of MUC1 in a preclinical model where MUC1 is endogenously expressed and functioning and will enable us to tailor more effective and safe MUC1 vaccination strategies. (supported by NIH grants T32CA82084 and RO1CA56103; J.G. by grants from CBCRA/CCS)

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 score0.005
Threshold uncertainty score0.017

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.000
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0050.001

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 head0.018
GPT teacher head0.267
Teacher spread0.249 · 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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