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Novel T cell therapy using spherical nucleic acids

2018· article· en· W4313359694 on OpenAlexaff
Donye Dominguez, Natalia Chernyak, Monica Guan, Alan Long, Andrew Lee, Yushang Chou, Siqi Chen, Lei Qin, Jie Fan, Chad Mirkin, Bin Zhang

Bibliographic record

VenueThe Journal of Immunology · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Interference and Gene Delivery
Canadian institutionsWestern University
Fundersnot available
KeywordsAntigenImmune systemT cellAntigen-presenting cellOligonucleotideAntigen presentationEpitopeCytotoxic T cellAdjuvantCell biologyBiologyChemistryMolecular biologyImmunologyBiochemistryIn vitro

Abstract

fetched live from OpenAlex

Abstract Immune stimulating Spherical Nucleic Acids (SNAs) are nanoparticles comprised of a spherical, hollow, lipid core surrounded by an oligonucleotide shell, allowing for the simultaneous delivery of tumor antigens and immune stimulating oligonucleotides into immune cells. Interestingly, we have found that SNAs can readily enter primary nonphagocytes such as T lymphocytes. The uptake of SNAs increases expression of co-stimulatory molecules and presentation of antigen via MHC class I molecules by T cells. SNA treated T cells are endowed with the ability to prime tumor antigen specific CD8+T cells in a long lasting and durable manner compared to "free" oligonucleotide and antigen admix-treated T cells. Furthermore, SNA treated T cells are able to act as cellular chaperones and transfer both SNA-derived oligonucleotide and antigen to other cells. In an amplifying cascade manner, these "bystander" cells, which receive SNA material, then gain the ability to prime antigen-specific CD8+ T cells and achieve stronger antitumor effect. The cellular chaperone cascade only occurs when cells are treated with SNAs compared to the "free" material. The unique structural properties of SNAs thus confer a set of key biological properties that make SNAs particularly compelling for the efficient and specific delivery of tumor antigen and adjuvant in adoptive T cell therapy.

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 score0.001
Threshold uncertainty score0.003

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.022
GPT teacher head0.262
Teacher spread0.241 · 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".

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Citations0
Published2018
Admission routes1
Has abstractyes

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