Abstract 3548: Oncolytic adenovirus Ad5dlE1b replication efficiency is dependent on p53 mutation type in cancer cells
Bibliographic record
Abstract
Abstract Adenoviruses are the most popular viral DNA vectors in the development of gene therapies and oncolytic therapy. Oncolytic adenoviruses are genetically modified to provide a means of tumor-selectivity by conditionally replicating in tumor cells and substantially killing them via their viral lytic cycle. The p53 molecule is a tumor suppressor protein that regulates the genomic integrity of the cell by controlling apoptosis and cell cycle events. Upon viral infection, normal cell (p53 intact cell) responds through the activation of apoptosis by the p53 dependent pathway. The adenovirus E1B 55kDa protein inactivates p53 and prevents apoptosis leading to progressive viral lytic cycle. Although demonstrating a moderate successes rate in some cancers, Ad deleted E1B 55kDa has not been approved as a standard therapy for all cancer types. Several studies have revealed that E1B deleted Ad replication was independent of p53 status in the cell, as the virus replicated better in some p53 deficient cancers more than others. However, this relationship has not been investigated deeply on the molecular level. However, this relationship has not been investigated deeply on the molecular level. Therefore, the objective of this study is to understand the correlation between p53 status, levels, and functional activity, and oncolytic Ad5dl E1B 55kDa replication efficiency at the molecular level. We evaluated the effect of p53's functional status on the replication efficiency of oncolytic Ad5dl E1B 55kDa. Multiple mutant p53 were engineered and viral growth was evaluated with each mutant form in H1299 cells. P53-R175H mutant successfully rescued viral growth and its transcriptome analysis showed partial loss of wild type activity as well as gain of new function by allowing the virus to grow and to exert its mechanism of selectivity. The mechanism entailed deregulating the expression of specific cellular genes in the p53 pathway, cell cycle and apoptosis, to promote its production leading to efficient oncolytic effect. These results confirmed that onclytic Ad5dl E1B 55kDa sensitivity is mutation type-specific. Therefore, before it is applied clinically as cancer therapy for p53 deficient tumors, the type of p53 mutation must be determined and also more screening for the effect of other mutations should be done for successful rescuing and efficient antitumor effect. Citation Format: Moemen Abdalla, Basma M. Abbas, Yousef Haj-Ahmad. Oncolytic adenovirus Ad5dlE1b replication efficiency is dependent on p53 mutation type in cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3548. doi:10.1158/1538-7445.AM2015-3548
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
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".