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Record W3216151293 · doi:10.1093/neuonc/noab196.692

EXTH-53. ANTI-ROBO1 CAR T CELLS EFFECTIVELY TARGET MALIGNANT BRAIN CANCER

2021· article· en· W3216151293 on OpenAlexaff
Chirayu Chokshi, Benjamin Brakel, Martín A. Rossotti, Chitra Venugopal, Sabra K. Salim, Darin Bloemberg, Parvez Vora, Kevin A. Henry, Sheila K. Singh

Bibliographic record

VenueNeuro-Oncology · 2021
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsNational Research Council CanadaMcMaster University
Fundersnot available
KeywordsDownregulation and upregulationCancer researchChimeric antigen receptorGliomaCancerDegranulationMedicineAntigenAntibodyBrain tumorCancer cellImmunologyImmunotherapyBiologyReceptorPathologyInternal medicineGene

Abstract

fetched live from OpenAlex

Abstract No standardized treatment exists for patients with recurrent glioblastoma (GBM). Given the aggressive nature of the disease and difficulty in modeling tumor recurrence, minimal efforts have been made to design rational therapies against it. The roundabout guidance receptor 1 (ROBO1) protein is involved in axonal guidance during neurodevelopment and is aberrantly upregulated in glioma where it mediates glioma cell migration. Here, we present that ROBO1 is highly expressed on the surface of malignant and treatment-refractory brain tumor initiating cells (BTICs), prompting the development of an anti-ROBO1 CAR-T cell therapy. Using the binding region of a single-domain antibody targeting ROBO1, we developed second-generation anti-ROBO1 CAR-T cells specific and effective against ROBO1-expressing BTICs. Upon antigen exposure, anti-ROBO1 CAR-T cells upregulated markers of activation and degranulation. Additionally, treatment of orthotopic and patient-derived brain tumor xenograft models with anti-ROBO1 CAR-T cells resulted in reduced tumor burden and prolonged survival, demonstrating the therapy’s therapeutic potential for treating neoplastic brain malignancies.

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 score0.002
Threshold uncertainty score0.007

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 integrity0.0000.001
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 head0.029
GPT teacher head0.349
Teacher spread0.320 · 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

Citations1
Published2021
Admission routes1
Has abstractyes

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