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On-target off-tumor toxicity from HER2-targeting chimeric antigen receptor (CAR) engineered T cell therapy: current solutions

2025· article· en· W4406226722 on OpenAlex
Zilei Wang

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueTheoretical and Natural Science · 2025
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsMcMaster University
Fundersnot available
KeywordsChimeric antigen receptorToxicityCurrent (fluid)AntigenCancer researchReceptorCell therapyCAR T-cell therapyMedicineImmunotherapyCellImmunologyBiologyInternal medicineImmune systemEngineeringBiochemistry

Abstract

fetched live from OpenAlex

One of the biggest threats to women’s lives and health is breast cancer, with HER2+ breast cancer accounting for a significant proportion of cases. This subtype is characterized by aggressive behavior, a high recurrence rate, and generally poor prognosis. While traditional HER2-CAR-T cell therapy has proven to show great success in treating HER2+ breast cancer, it carries the risk of on-target off-tumor toxicity, which could be life-threatening for patients. This review outlines the challenges associated with traditional HER2-CAR-T cell therapy and explores current strategies aimed at mitigating on-target off-tumor toxicity. The review categorizes these strategies into three main approaches, providing a comprehensive overview to help the medical and research community better understand the current state and future directions of HER2-CAR-T cell therapy. By discussing these approaches and the underlying mechanisms that make them effective, this review aims to inspire further innovation in improving existing HER2-CAR-T cell therapies. A thorough understanding of the current challenges and promising avenues for enhancement in HER2-CAR-T cell therapy is essential for advancing future research and clinical applications.

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.

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)0.001
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 score0.040
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.011
GPT teacher head0.290
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