Abstract 2836: Metronomic cyclophosphamide enhances antitumor immune response induced by a DepoVaxTM-based peptide vaccine.
Notice bibliographique
Résumé
Abstract Advanced cancers utilize several mechanisms to escape immune-mediated detection and destruction thus reducing the effectiveness of cancer therapeutics on multiple levels. Low dose cyclophosphamide (CPA) has been investigated as an immune modulator to potentiate active immune response towards tumor cells, but a single bolus injection of CPA has been ineffective at boosting response to cancer vaccines in most clinical trials. We sought to determine if a metronomic regimen of low dose CPA (mCPA) could enhance the efficacy of a peptide-based vaccine formulated in DepoVaxTM (DPX). DPX is a novel vaccine platform comprised of liposomes in oil that is formulated with an adjuvant, universal T-helper peptide and specific tumor peptide antigens. Using a murine tumor model (C3) we tested the benefit of combining mCPA and vaccination for controlling well established subcutaneous solid tumors in vivo. Mice were treated starting 5 days after C3 tumor implantation with mCPA administered in drinking water in a one week on/ off schedule and vaccinated every 3 weeks. In this model, neither mCPA nor vaccine treatments alone were sufficient to eradicate advanced tumors. However, combining mCPA with vaccination provided effective tumor control. Ex vivo analysis of immune response after a single treatment of mCPA combined with vaccine showed a significant increase in antigen-specific IFN-γ release by ELISPOT, which became more pronounced after multiple rounds of treatment in tumor bearing mice. This immune response was accompanied by a corresponding increase in antigen-specific cytotoxic T cell activity as measured by in vivo CTL assay. Dextramer analysis of the antigen-specific CD8+ T cells in the vaccine-draining lymph node revealed that while the total number of CD8+ T cells decreased with mCPA treatment, the number of antigen-specific CD8+ T cells was increased by vaccination and not reduced by mCPA. Flow cytometric analysis of splenocyte cell populations did not show any significant reduction in CD4+CD25hiFoxP3+Treg populations due to mCPA treatment, as previously reported by others, but we did find an increase in myeloid-derived suppressor cells due to mCPA treatment that was decreased in mice treated with both mCPA & vaccination. Finally, adoptive transfer of T cells from tumor bearing mice treated with mCPA & vaccination significantly reduced tumor growth in tumor challenged recipients. Overall, our data indicate that mCPA combines with a peptide based DPX vaccine to enhance the T cell response to antigen that ultimately results in an improved immunotherapy for cancer. The immune-enhancing effects of mCPA in this model are multi-faceted and augment the T cell responses independent of direct cytotoxic effects on the tumor. The results of this pre-clinical study have assisted in the designing of a phase II clinical trial for DPX-Survivac vaccine in combination with mCPA in ovarian cancer patients. Citation Format: Genevieve M. Weir, Marianne M. Stanford, Neil L. Berinstein, Mohan Karkada, Robert S. Liwski, Marc Mansour. Metronomic cyclophosphamide enhances antitumor immune response induced by a DepoVaxTM-based peptide vaccine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2836. doi:10.1158/1538-7445.AM2013-2836
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 ».