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Record W4306179806 · doi:10.1038/s41467-022-33597-y

Nanoparticle-based modulation of CD4+ T cell effector and helper functions enhances adoptive immunotherapy

2022· article· en· W4306179806 on OpenAlexfundno aff
Ariel Isser, Aliyah B. Silver, Hawley C. Pruitt, Michal Mass, Emma H. Elias, Gohta Aihara, Si-Sim Kang, Niklas Bachmann, Yingyu Chen, Elissa K. Leonard, Joan Glick Bieler, Worarat Chaisawangwong, Joseph Choy, Sydney R. Shannon, Sharon Gerecht, Jeffrey S. Weber, Jamie B. Spangler, Jonathan P. Schneck

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsnot available
FundersBloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins UniversityNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNatural Sciences and Engineering Research Council of CanadaJohns Hopkins Bloomberg School of Public HealthDepartment of Pathology, Johns Hopkins UniversityNewfoundland and LabradorNational Institute of Biomedical Imaging and BioengineeringSidney Kimmel Comprehensive Cancer CenterEmerson CollectiveMaryland Stem Cell Research FundJohns Hopkins UniversityU.S. Department of Health and Human ServicesNational Institutes of HealthNational Science FoundationU.S. Department of Defense
KeywordsCytotoxic T cellBiologyCell biologyAntigen-presenting cellCD8Major histocompatibility complexT cellStreptamerImmunotherapyAntigenImmunologyEffectorMHC class IICancer researchImmune systemIn vitroBiochemistry

Abstract

fetched live from OpenAlex

Abstract Helper (CD4 + ) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8 + ) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansion of antigen-specific CD4 + T cells hinders consistency and scalability of CD4 + T cell-based therapies, and complicates mechanistic studies. Here we describe a nanoparticle platform for ex vivo CD4 + T cell culture that mimics antigen presenting cells (APC) through display of major histocompatibility class II (MHC II) molecules. When combined with soluble co-stimulation signals, MHC II artificial APCs (aAPCs) expand cognate murine CD4 + T cells, including rare endogenous subsets, to induce potent effector functions in vitro and in vivo. Moreover, MHC II aAPCs provide help signals that enhance antitumor function of aAPC-activated CD8 + T cells in a mouse tumor model. Lastly, human leukocyte antigen class II-based aAPCs expand rare subsets of functional, antigen-specific human CD4 + T cells. Overall, MHC II aAPCs provide a promising approach for harnessing targeted CD4 + T cell responses.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.499
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.320
Teacher spread0.298 · 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 teacher head, not a consensus.

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

Citations26
Published2022
Admission routes1
Has abstractyes

Explore more

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