Abstract 1449: MG1 Maraba boost following adenovirus prime generates tumor antigen-specific T cells which are potentiated by anti-PD-1 antibody combination
Notice bibliographique
Résumé
Immune checkpoint inhibitors, such as antibodies blocking PD-1 and PD-L1, have been shown to potentiate pre-existing immune responses and improve patient survival. MG1 Maraba is a novel oncolytic virus that we bioselected and engineered to cause cancer cell death through two distinct and complementary mechanisms-of-action, direct cancer lysis and tumor-antigen specific T cell generation. MG1 Maraba encoding tumor antigens has been demonstrated to boost pre-existing immune responses. We are currently using a non-replicating adenovirus as the priming entity in our ongoing preclinical and clinical studies for our MG1 Maraba product candidates. This therapeutic platform is able to generate a large number of highly-functional antigen-specific T cells, in addition to its oncolytic activity, in mice, non-human primates (NHP) and patients treated with Adenovirus and oncolytic MG1 Maraba, expressing the same tumour associated antigen. This study investigates the ability of αPD-1 to potentiate immune responses generated by Ad/MG1 prime/boosting, and whether the timing of αPD-1 administration impacts the immune responses and therapeutic outcome. The combination of αPD-1 and Ad/MG1 treatment was investigated in a challenging murine model of metastatic melanoma. In three independent experiments, mice bearing advanced B16F10 lung metastases treated with Ad/MG1-hDCT in combination with αPD1 antibody, overall survival was increased to greater than 90%, compared to survival rates of less than 40% in mice treated with Ad/MG1-hDCT alone. The increased efficacy was correlated with improved anti-tumour immune responses in the αPD-1 combination group. The strongest effects of αPD-1 were observed when αPD-1 treatment was initiated immediately following Ad-hDCT immunization leading to significantly increased anti-tumour immune responses at all timepoints analyzed. When delayed until 1 week after MG1 treatment, αPD-1 was unable to improve the anti-tumour immune responses, or therapeutic efficacy, elicited by Ad/MG1 treatment. Similar effects were observed using an αPD-L1 targeted antibody. Therefore, the timing of PD-1/L1 blockade during Ad/MG1 treatment was determined to be a critical parameter for successful therapeutic outcomes. In addition, a non-human primate study is underway to assess the combination of αPD-1 with Ad/MG1-E6E7 (expressing HPV E6 and E7) when delivered concurrent with adenovirus immunization. Moreover, these data highlight the timing of checkpoint inhibitor treatment as a critical parameter for consideration when administering immune checkpoint inhibitors with other agents, including oncolytic viral immunotherapies.Citation Format: Kyle Stephenson, Kwame Twumasi-Boateng, Amy Patrick, Caroline Breitbach, Michael Burgess, Brian Lichty. MG1 Maraba boost following adenovirus prime generates tumor antigen-specific T cells which are potentiated by anti-PD-1 antibody combination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1449.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,002 |
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; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».