Abstract 2274: An immune-educating therapy, Maveropepimut-S, elicits a diverse and active anti-tumor T cell response in patients with advanced recurrent ovarian cancer
Notice bibliographique
Résumé
Abstract Maveropepimut-S (MVP-S) is a T cell activating immunotherapy designed within the novel DPX® immune delivery platform. MVP-S is comprised of 5 HLA class I peptides from the tumor antigen, survivin, along with the A16L T helper peptide, and the innate immune activator, polydIdC. Analysis of PBMCs collected from advanced recurrent ovarian cancer patients treated with MVP-S based therapy in the DeCidE1 trial (NCT02785250) showed robust survivin-specific T cell induction that persisted in some patients up to 420 days. Herein, we analyzed the T cell repertoires of pre- and on-treatment (on-Tx) tumor biopsies from these patients to further investigate the fate of T cells elicited by the MVP-S based therapy. Analysis of the T cell receptor beta (TCRβ) sequences revealed that MVP-S treatment actively promotes the infiltration of a new, diverse T cell repertoire with 51.6% to 94.9% new clones recruited to the on-Tx tumors. These novel clones cumulatively comprise 29.8% to 90.5% of the total intra-tumoral T cell population. Profiling of patients achieving partial response (by RECISTv1.1) versus those achieving only progressive disease indicated an increase in clonal diversity, with reduction in clonal domination, in the on-Tx tumors, suggestive of epitope spreading in these responsive patients. To evaluate frequency of survivin-specific T cells within the tumor tissue, a library of survivin-specific T cell clonotypes was prepared using in vitro expanded and sorted PBMCs. Across 33 patients of various clinical outcomes and timepoints, 309 unique, survivin-specific clones were identified. Clonotypes were found to be strongly subject-specific with very limited overlap across subjects. TCRβ sequences of circulating survivin-specific T cells were compared with TCβ repertoire in the tumor biopsies to determine clonal sequence overlap. Sixty-four of the identified survivin-specific clones (20.7%) were found in tumor samples (pre- and on-treatment); of these, 71.9% (46/64) were detected in on-treatment samples only, compared to 12.5% (8/64) in pre-treatment samples only. Importantly, survivin-specific clones were recurrently found within the top 1-10% of the most frequent clones in the on-treatment tumoral T cell population, suggesting that MVP-S therapy promoted strong enrichment and expansion of survivin-specific T cells within tumour tissue. These data indicate that treatment of advanced recurrent ovarian cancer patients with MVP-S based therapy induced robust, persistent survivin-specific T cells that were detected in circulation up to 420 days. These de novo elicited T cells were demonstrated to migrate into tumor tissues, where MVP-S therapy promoted reinvigoration of the total T cell population with new highly diverse clones including strong expansion of survivin-specific T cells. Citation Format: Kelcey Patterson, Barry Kennedy, Walead Ebrahimizadeh, Aurelio Lobo, Heather Hirsch, Heather Torrey, Valarmathy Kaliaperumal, Lisa MacDonald, Jeremy Graff, Stephan Fiset, Olga Hrytsenko. An immune-educating therapy, Maveropepimut-S, elicits a diverse and active anti-tumor T cell response in patients with advanced recurrent ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2274.
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».