PDTM-46. POLIOVIRUS RECEPTOR (CD155) EXPRESSION IN PEDIATRIC BRAIN TUMORS MEDIATES ONCOLYSIS OF MEDULLOBLASTOMA AND PLEOMORPHIC XANTHOASTROCYTOMA
Bibliographic record
Abstract
Poliovirus oncolytic viral immunotherapy is a putatively novel approach to treat both low grade and malignant pediatric brain tumors. However, the expression of the poliovirus receptor (PVR), CD155, on a variety of pediatric brain tumors and its ability to infect, propagate, and lyse pediatric brain tumor cells is unknown. CD155 expression in a variety of pediatric tumor specimens including pleomorphic xanthoastrocytoma (PXA), medulloblastoma, atypical teratoid rhabdoid tumor, embryonal tumor, and anaplastic ependymoma was assessed using a validated rabbit monoclonal antibody. The ability of poliovirus:rhinovirus genetic recombinant, PVSRIPO, to infect PXA (645 [BRAF V600E mutation] and 2363) and medulloblastoma (D283, D341) cell lines was determined by measurement of viral propagation and cell killing. Gene expression data from a medulloblastoma patient cohort of 763 patients was used to determine differential PVR mRNA expression and compared using analysis of variance. CD155 expression was present in 53 of 57 patient specimens analyzed in all PXA and medulloblastoma cell lines. One-step growth curves of PVSRIPO at a multiplicity of infection of 10 demonstrated productive infection and peak plaque formation units at 5–10 hours. PVSRIPO infection of all four cell lines demonstrated decreased proliferation in 2363, 645, and D341 cell lines at 48 hours (p<0.001) and resulted in cell death. PVR expression was significantly highest in Group 3γ, WNTα, and WNT (subgroups with c-myc overexpression) compared to the other medulloblastoma subtypes (p<0.001). CONCLUSIONS: Poliovirus receptor, CD155, is widely expressed in a variety of brain tumor specimens. This proof-of-concept in vitro study demonstrated that PVSRIPO was capable of infecting, propagating, and prohibiting cell proliferation in PXA with and without BRAF V300E mutations and Group 3 medulloblastoma. Future studies will evaluate PVSRIPO to treat pediatric brain tumors and the possible link between c-myc and PVR expression.
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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) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".