Non-replicating rhabdovirus-derived particles (NRRPs) eradicate acute leukemia by direct cytolysis and induction of antitumor immunity
Bibliographic record
Abstract
Rhabdoviruses (RVs) are currently being pursued as anticancer therapeutics for various tumor types, notably leukemia. However, modest virion production and limited spread between noncontiguous circulating leukemic cells requires high-dose administration of RVs, which exceeds the maximum tolerable dose of the live virus. Furthermore, in severely immunosuppressed leukemic patients, the potential for uncontrolled live virus spread may compromise the safety of a live virus approach. We hypothesized that the barriers to oncolytic virotherapy in liquid tumors may be overcome by administration of high-dose non-replicating RVs. We have developed a method to produce unique high-titer bioactive yet non-replicating rhabdovirus-derived particles (NRRPs). This novel biopharmaceutical is multimodal possessing direct cytolytic and immunomodulatory activity against acute leukemia. We demonstrate that NRRP resistance in normal cells is mediated by intact antiviral defences including interferon (IFN). This data was substantiated using murine models of blast crisis. The translational promise of NRRPs was demonstrated in clinical samples obtained from patients with high-burden multidrug-resistant acute myeloid leukemia. This is the first successful attempt to eradicate disseminated cancer using a non-replicating virus-derived agent, representing a paradigm shift in our understanding of oncolytic virus-based therapies and their application toward the treatment of acute leukemia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".