Abstract LB-283: JX-594, a targeted multi-mechanistic oncolytic poxvirus, selectively infects tumor vasculature and causes acute tumor vascular disruption and necrosis in advanced cancer patients
Bibliographic record
Abstract
Abstract JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell cycle abnormalities and epidermal growth factor receptor (EGFR)/ras pathway activation. Direct oncolysis plus granulocyte macrophage -colony stimulating factor (GM-CSF) expression also stimulates anti-tumoral immunity. JX-594 infection was evaluated in vitro on human umbilical vein endothelial cells (HUVECs) and by immunohistochemical analysis in tumor biopsies from JX-594 treated (intravenous administration) patients with advanced, treatment-refractory solid tumors. JX-594 associated changes in tumor perfusion were also assessed in patients by dynamic contrast-enhanced magnetic resonance imaging (dce-MRI; at baseline and Day 5 after intratumoral JX-594 administration). In vitro susceptibility of HUVECs to JX-594 infection was shown to be dependent on vascular endothelial growth factor (VEGF) stimulation. Furthermore, JX-594 was capable of infecting tumor-associated endothelial cells after intravenous infusion in patients with advanced solid tumors. No clinical evidence of normal vasculature infection or toxicity was noted. Tumor perfusion was significantly decreased within 5 days post JX-594 treatment, including in hepatocellular carcinoma and colorectal cancer metastases. Perfusion was markedly reduced in both directly injected and distant non-injected tumors. Choi (necrotic) responses at later timepoints were demonstrated. In addition to targeting cancers by direct infection and lysis of tumor cells, JX-594 is capable of directly infecting VEGF-stimulated/tumor-associated endothelial cells. By targeting tumor-associated vasculature, JX-594 acutely disrupts the tumor's blood supply leading to tumor destruction. Targeted oncolytic poxviruses such as JX-594 represent a novel and highly selective class of vascular disrupting agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-283. doi:10.1158/1538-7445.AM2011-LB-283
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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) | 0.002 | 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".