Abstract 596: Oncolytic vesicular stomatitis virus selectively kills bladder cancer cells which have a low level of type I interferon receptor
Bibliographic record
Abstract
Abstract Bladder cancer is the second most common genitourinary malignancy. Current treatments options are of limited efficacy since approximately 80% of patients will develop recurrent tumors of which 20-30% evolve into more aggressive, potentially lethal cancers. A new strategy to treat bladder cancer is the intra-vesical application of vesicular stomatitis virus (VSV), which is a replication competent oncolytic virus that relies on an aberrant interferon signaling pathway within cancer cells. Using a tissue microarray composed of human bladder cancer cores and by immunohistochemistry, we observed that expression of type I interferon (IFN) receptor (IFNAR) was decreased relative to normal bladder tissue. Advanced bladder cancers had even lower expression of IFNAR. We observed that VSV preferentially targeted high grade bladder cancer cells which were resistant to type I IFN treatment. We also found that these high grade bladder cancer cells susceptible to VSV-induced lysis had low expression of IFNAR. Furthermore, siRNA knockdown of IFNAR indeed facilitated replication of VSV in cells previously resistant to VSV treatment. Consequently, intra-vesicular instillation of wildtype VSV and the Delta51M strain, which has an impaired ability to shutdown innate immunity, significantly inhibited high grade tumor growth by 98% and 90% respectively as compared to controls treated with UV-inactivated VSV. No evidence of toxicity or systemic viral infection in either group was found. In conclusion, down-regulation of IFNAR in bladder cancer may be one of the primary molecular mechanisms for clinical IFN resistance. However, this also facilitates VSV replication and oncolysis in high risk bladder cancers and provides a basis for selecting bladder cancer patients for IFN or oncolytic VSV therapy in future clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 596.
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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".