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Record W2913977629 · doi:10.1016/j.omtm.2019.01.012

Quantifying Antigen-Specific T Cell Responses When Using Antigen-Agnostic Immunotherapies

2019· article· en· W2913977629 on OpenAlexafffund
Jacob P. van Vloten, Lisa A. Santry, Thomas M. McAusland, Khalil Karimi, Grant McFadden, Jim Petrik, Sarah K. Wootton, Byram W. Bridle

Bibliographic record

VenueMolecular Therapy — Methods & Clinical Development · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsUniversity of Guelph
FundersNatural Sciences and Engineering Research Council of CanadaTerry Fox Research Institute
KeywordsAntigenImmunogenicityImmunotherapyImmune systemEpitopeCancer immunotherapyImmunologyMajor histocompatibility complexT cellTumor antigenCytotoxic T cellCD8BiologyCancer researchMedicineComputational biologyIn vitro

Abstract

fetched live from OpenAlex

Immunotherapies are at the forefront of the fight against cancers, and researchers continue to develop and test novel immunotherapeutic modalities. Ideal cancer immunotherapies induce a patient's immune system to kill their own cancer and develop long-lasting immunity. Research has demonstrated a critical requirement for CD8 + and CD4 + T cells in achieving durable responses. In the path to the clinic, researchers require robust tools to effectively evaluate the capacity for immunotherapies to generate adaptive anti-tumor responses. To study functional tumor-specific T cells, researchers have relied on targeting tumor-associated antigens (TAAs) or the inclusion of surrogate transgenes in pre-clinical models, which facilitate detection of T cells by using the targeted antigen(s) in peptide re-stimulation or tetramer-staining assays. Unfortunately, many pre-clinical models lack a defined TAA, and epitope mapping of TAAs is costly. Surrogate transgenes can alter tumor engraftment and influence the immunogenicity of tumors, making them less relevant to clinical tumors. Further, some researchers prefer to develop therapies that do not rely on pre-defined TAAs. Here, we describe a method to exploit major histocompatibility complex expression on murine cancer cell lines in a co-culture assay to detect T cells responding to bulk, undefined, tumor antigens. This is a tool to support the preclinical evaluation of novel, antigen-agnostic immunotherapies.

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)0.002
metaresearch head score (Gemma)0.001
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 score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.002
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 head0.136
GPT teacher head0.415
Teacher spread0.279 · 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

Citations18
Published2019
Admission routes2
Has abstractyes

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