Abstract LBA030: DPX-SurMAGE, a novel dual-targeted immunotherapy for bladder cancer, induces target-specific T cells with a favorable safety profile in preclinical model
Notice bibliographique
Résumé
Abstract Thirty to forty percent of high-risk non-muscle invasive bladder cancer (NMIBC) fail standard of care, leaving radical cystectomy as the most recommended option for these patients. Therefore, new efficient and tolerable treatments are required to prevent or delay cystectomy. The DPX platform 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. Peptides that are packaged in DPX are specifically taken up by APCs. Maveropepimut-S (MVP-S, formerly known as DPX-Survivac) incorporates 5 HLA-restricted peptides derived from the anti-apoptotic protein survivin and is the first DPX-based immunotherapy. MVP-S demonstrated survivin-specific and sustained T cell response along with clinical activity and limited adverse events in patients with solid and hematologic tumors. Survivin and MAGE-A9 are well characterized tumor-associated antigens (TAAs) frequently overexpressed in bladder tumours. The DPX platform was leveraged to develop a new dual-targeted T cell activating immunotherapy, DPX-SurMAGE, incorporating HLA-A2 restricted peptides of both survivin and MAGE-A9. The feasibility of packaging peptides targeting two different TAAs into the DPX platform was assessed by performing comparative immunogenicity evaluation between 2 MVP-S peptides and DPX-SurMAGE in HLA-A2 transgenic mice. The magnitude of peptide-specific T cell responses against the shared HLA-A2 survivin peptide was similar in animals immunized with either DPX-SurMAGE or MVP-S indicating that the presence of MAGE-A9 peptides did not affect the immunogenicity of the MVP-S-based survivin peptide in the DPX-SurMAGE formulation. Immunogenicity and toxicity of DPX-SurMAGE with and without metronomic cyclophosphamide (mCPA) was further evaluated. IFN-γ ELISPOT assessment demonstrated robust induction of peptide-specific T cell responses to survivin and MAGE-A9 peptide pools. These strong responses were maintained at similar levels in the long-term chronic phase of the assessments both with and without mCPA. Preliminary safety observations including Detailed Clinical Examination (DCE), body weights and organ weights showed no sign of toxicity nor significant changes in mice treated with DPX-SurMAGE with or without mCPA. There were no significant differences in injection site reactions between DPX-SurMAGE groups (with and without mCPA). The local injection site reactions for DPX-SurMAGE groups were comparable to that of DPX-Empty control group. This study demonstrates the unique ability of the DPX delivery platform to deliver multiple antigenic TAA peptides without compromising the immunogenicity of each peptide. Furthermore, the DPX-SurMAGE treatment was well tolerated and was shown to induce robust and sustained target-specific T cell responses against both survivin and MAGE-A9 antigens, supporting the impending phase 1 clinical trial in high risk NMIBC patients. Citation Format: Valérie Picard, Valarmathy Kaliaperumal, Fanny Gaignier, Marjorie Besançon, Yogesh Bramhecha, Olga Hrytsenko, Alecia McKay, Stephan Fiset, Alain Bergeron, Yves Fradet. DPX-SurMAGE, a novel dual-targeted immunotherapy for bladder cancer, induces target-specific T cells with a favorable safety profile in preclinical model [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 LBA030.
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 | 0,001 |
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 ».