Abstract B077: Evaluating oncolytic vaccines targeting mutated epitopes in a murine fibrosarcoma model CMS-5
Notice bibliographique
Résumé
Abstract Oncolytic viruses have traditionally been used as stand alone therapy delivered to animals and patients to lytically destroy tumor tissue. However, it has recently become clear that involvement of the immune system is an extremely important aspect of these therapies. To further enhance anti-tumor immune responses we have utilized an oncolytic vaccine approach. This approach involves priming the immune system to a specific tumor associated antigen (TAA) with an Adenovirus and then subsequently delivering an oncolytic Rhabdovirus expressing the same tumor antigen leading to robust anti-tumor immune responses and improved efficacy. For the studies presented herein we have developed oncolytic vaccines targeting mutated epitopes expressed in CMS-5. Immune responses generated towards these epitopes through oncolytic vaccination will be characterized and their ability to control tumor growth will be evaluated. We hypothesize that the foreign nature of these mutated epitopes will allow for the generation of substantial immune responses following oncolytic vaccination in tumor bearing mice. In preliminary studies, oncolytic vaccination has been able to generate robust immune responses leading to as many as 60% of circulating CD8+ T cells responding to a single mutated epitope in tumor free animals. Therapeutic oncolytic vaccination of CMS-5 tumor bearing animals was still able to generate large anti-tumor immune responses, however these responses were cut in half compared to tumor free animals. The resultant anti-tumor immune response was able to significantly control tumor growth, and the magnitude of these responses correlated with survival. Even though there was a delay in tumor growth following therapy, the responses were not durable and all mice ultimately failed the therapy. We are currently engaged in studies to further characterize the immune responses generated and determine what, if any, immunosuppression led to failure of our therapy; even in the presence of anti-tumor immune responses exceeding 20% of peripheral CD8+ T cells. Nanostring analysis of the tumor microenvironment are being conducted focusing on gene signatures for immune cells and inflammation and these data will be confirmed by histology and flow cytometry. These studies will help shed light on potential mechanisms of immune evasion/suppression following oncolytic vaccination and point to potential targets for modulation of the oncolytic vaccine induced immune response. Citation Format: Kyle Stephenson, Matthew Atherton, John Bell, Brian Lichty. Evaluating oncolytic vaccines targeting mutated epitopes in a murine fibrosarcoma model CMS-5. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B077.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».