NT-02 * EARLY TREATMENT OF HER2-AMPLIFIED BRAIN TUMOURS WITH TARGETED NK-92 CELLS AND FOCUSED ULTRASOUND IMPROVES SURVIVAL
Bibliographic record
Abstract
Malignant brain tumors have a dismal prognosis. Microscopic and often macroscopic residual remain after surgical resection, necessitating adjuvant chemo- and radiotherapy. Many intravenously delivered chemotherapeutic agents are hindered by the cerebral capillary endothelium and blood brain barrier (BBB), either due to their size, lipophilicity, or their interaction with efflux channels, resulting in modest treatment efficacy. Both those chemotherapeutic agents that cross the BBB and radiotherapy result in significant damage to healthy brain tissue. We previously demonstrated that targeted Natural Killer (NK-92) cells could be delivered to focal regions of the brain using a combination of focused ultrasound and Definity microbubbles. Targeted NK cells have advantages over other systemic therapies including their specific cytotoxicity to malignant cells, particularly those expressing the target antigen, in addition to sparing healthy cells and being unaffected by efflux channels. As such, once these cells gain access to the CNS, they can track to malignant tissues without inflicting collateral damage. We investigated whether multiple combined treatments of targeted NK-92 cells and focused ultrasound with microbubbles could slow tumor growth and improve survival in an orthotopic HER2-amplified rodent brain tumor model, using a human breast cancer line as a prototype. The HER2 receptor is expressed by a number of epithelial tumours including breast and glioblastoma. Breast cancers with HER2 amplification are more aggressive, have a higher risk of CNS metastasis, and poorer prognosis. We found that early intensive treatment with targeted NK-92 cells and ultrasound improved survival compared with bi-weekly treatments, or either treatment alone. The intensive treatment paradigm resulted in cure in 50% of subjects. Many tumour proteins could be exploited for targeted therapy with the NK-92 cell line, and combined with the mounting safety evidence for trans-cranial ultrasound, this may soon provide a non-invasive and highly targeted treatment option for patients with brain tumours.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".