Abstract A034: VV-iVP55: A Superior Vaccinia Virus Platform with Enhanced Oncolytic Potency and Immunogenicity
Bibliographic record
Abstract
Abstract This research introduces VV-iVP55, a conditionally replicating vaccinia virus platform, as a promising alternative to thymidine kinase (Tk) deleted oncolytic vaccinia viruses. The unique feature of VV-iVP55 is its growth control using doxycycline, a trait not found in conventional Tk-deleted viruses. Laboratory studies revealed that VV-iVP55 achieves higher virus titers and lower cell viability in B16-F10 and MC38 syngeneic models compared to Tk-deleted viruses. Notably, VV-iVP55 demonstrated lower toxicity in immunocompromised mice upon doxycycline withdrawal, unlike Tk-deleted viruses that showed significant toxicity. In vivo efficacy studies further highlighted the superiority of VV-iVP55 over Tk-deleted viruses in CT26 and B16 subcutaneous models, as well as MC38 subcutaneous and intraperitoneal models. An immune microenvironment analysis conducted six days post-intratumoral injection revealed beneficial alterations induced by VV-iVP55, such as increased T and B cell content in the tumor and reduced MDSCs in both the tumor and spleen. Moreover, VV-iVP55 was linked to a significant change in T cell differentiation. Unlike the PBS and Tk viruses, which showed almost complete differentiation towards effector T cells, VV-iVP55 maintained a substantial population of T cells in naive and transition phases, significantly in both CD4 and CD8 T cells. This likely led to lower expression of exhaustion markers PD1, TIM3, TIGIT, and LAG3, suggesting less exhaustion and more potential for immune response. In summary, VV-iVP55 emerges as a powerful alternative to Tk-deleted oncolytic vaccinia viruses, offering enhanced immunogenicity, controlled toxicity, and preserved oncolytic properties. Citation Format: Reza Rezaei, Taha Azad, Julia Petryk, John C. Bell. VV-iVP55: A Superior Vaccinia Virus Platform with Enhanced Oncolytic Potency and Immunogenicity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A034.
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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 | 0.001 |
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".