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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».