Prostate-specific expression of ICP4 complements ICP4(−) HSV-1 virus for oncolysis of prostate cancer cells
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 47, 2006 4025 Herpes simplex virus type-1 (HSV-1) has been demonstrated as a potent therapeutic viral vector for cancer treatment. The rationale for using replicative and oncolytic viruses is that viral replication in infected tumor cells will permit in situ viral multiplication and spread of an oncolytic viral infection throughout the tumor mass. The aim of our study was to demonstrate that an amplicon system containing a prostate-specific probasin promoter, ARR2PB upstream to an essential viral gene (ICP4), can complement a ICP4(−) HSV-1 virus for lytic replication specifically to prostate tumor cells. To prove this concept, two amplicon constructs, CMV-ICP4, and ARR2PB-ICP4 were packaged by the a replication deficient ICP4(−) helper virus. We tested the complementing ability, the therapeutic efficacy and the toxicity of the two amplicon viruses in LNCaP tumor cells. In vitro virus replication and tumor cell lysis assay were performed in various prostate tumor cells. Our results showed that the ARR2PB-ICP4 amplicon virus can complement the ICP4− helper virus to efficiently replicate and cause cell lysis in prostate cancer cell cultures. Intratumoral inoculation of both CMV-ICP4 and ARR2PB-ICP4 amplicon/helper virus system in subcutaneous LNCaP xenograft tumor mouse model showed a 70% ∼ 80% reduction in tumor size. However, the toxicity in non-tumor tissues was much lower for the ARR2PB-ICP4 amplicon than that of the CMV-ICP4 amplicon virus by Q-PCR and histological analysis of the organs collected from the virus treated mice. The residual toxicity of the ARR2PB-ICP4 amplicon virus could be completely eliminated by the additional gancyclovir (GCV) treatment. In conclusion, our results demonstrated that a replication deficient HSV-1 virus can be complemented by an amplicon to restore its oncolytic activity in a tumor specific fashion and therefore could be a potential use in oncolytic virus therapy for cancer. (Supported by a grant from the Terry Fox Foundation).
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".