Abstract LBA026: Survivin peptides formulated in the DPX delivery platform rather than standard emulsions, elicit a robust, sustained T cell response to survivin in advanced and recurrent ovarian cancer patients
Notice bibliographique
Résumé
Abstract Despite improvements in peptide-based tumor antigen discovery, success in eliciting a clinically meaningful T cell response to these peptides has been limited. The choice of antigen delivery platform strongly impacts the quality, quantity, and durability of induced immune responses. DPX is a unique, water-free, lipid-based formulation that can deliver peptides, proteins, and small molecules specifically to antigen presenting cells (APCs), eliciting a targeted, robust, and sustained T cell-based immune response. DPX allows for antigenic peptides to remain at the site of injection without significant diffusion into surrounding tissues, in direct contrast to most emulsion-based delivery methods. Maveropepimut-S (MVP-S; formerly known as DPX-Survivac) is a DPX formulation that incorporates 5 HLA-restricted peptides derived from the anti-apoptotic protein survivin, which is commonly overexpressed in advanced cancers including ovarian cancer. Prior efforts with these same peptides emulsified in Montanide ISA 51 VG provided limited clinical benefit and no objective responses (Lennerz 2014). We now show in pre-clinical models that, when packaged in DPX, these peptides elicit higher avidity, more abundant and cytolytically-active survivin-specific T cells than standard emulsion-based formulations. Early clinical studies with MVP-S in advanced ovarian cancer patients have shown a persistent, survivin-specific T cell response, which in a subset of patients lasted more than 2 years. The recently completed phase 2 study of MVP-S and low-dose cyclophosphamide (CPA) in advanced and recurrent ovarian cancer subjects (DeCidE1), provided encouraging clinical benefit across multiple measures (ORR = 26% & DCR = 79% on target lesions, mOS = 19.9 months in evaluable patients). We now show that majority of patients in this study had survivin-specific T cells on treatment by in vitro tetramer staining (87%) and ex vivo ELISPOT analyses (56%). Importantly, 75% of patients deriving clinical benefit had active survivin-specific T cells by ex vivo ELISPOT analyses. Immunophenotyping of the longitudinally collected PBMCs showed evidence of sustained T cell proliferation by tetramer staining across time and did not show increased expression of immunosuppressive markers (e.g., PD-1, Tim3), suggesting that MVP-S induced T cells remain active over time. TCRβ analyses of tumor TCR repertoires further showed the ability of de novo elicited survivin-specific T cells to infiltrate on-treatment tumours. Collectively, these preclinical and clinical data show that MVP-S treatment effectively elicits a robust, persistent, survivin-specific T cell response. These data also provide compelling evidence that clinical benefit in DeCidE1 patients is most evident in those with survivin-specific T cells. Finally, these data further underscore the unique capacity of DPX technology to effectively elicit peptide-specific, T cell based immune responses when conventional formulations do not. Citation Format: Yogesh Bramhecha, Oliver Dorigo, Valarmathy Kaliaperumal, Heather Torrey, Walead Ebrahimizadeh, Kelcey Patterson, Brennan Dirk, Moamen Bydoun, Barry Kennedy, Aurelio Lobo, Genevieve Weir, Jeremy Graff, Stephan Fiset, Olga Hrytsenko. Survivin peptides formulated in the DPX delivery platform rather than standard emulsions, elicit a robust, sustained T cell response to survivin in advanced and recurrent ovarian cancer patients [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA026.
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 ».