Abstract A16: A phase I/II clinical trial of a MUC1-glycopeptide dendritic cell vaccine in castrate resistant non-metastatic prostate cancer patients
Notice bibliographique
Résumé
Abstract Background: Current treatment options for prostate cancer (PCa) patients with rising PSA despite castrate testosterone levels are limited. A number of immunotherapeutic approaches for the treatment of PCa have been studied with varying efficacy. MUC1 has been an antigen of interest for immunotherapy, however, tolerance to the peptide epitopes has led to limited immune response. A glycosylated version of the antigen, Tn-100mer-MUC1, was shown to be effective in overcoming tolerance in pre-clinical studies. Dendritic cells (DC) take up and process Tn-100mer-MUC1 and present both glycopeptide and peptide epitopes. We report the results of a phase I/II clinical trial of an autologous DC vaccine loaded with Tn-100mer-MUC1 and KLH in patients with castrate resistant, non-metastatic PCa. Methodology: Eight consenting patients with rising PSA were enrolled into the study; however one patient progressed with bone metastases before receiving the first vaccine dose. To generate the autologous DC vaccine, patient's monocytes were elutriated from apheresis product and cultured under conditions suitable for the generation of mature and motile DCs. Tn-100mer-MUC1 glycopeptide and clinical-grade KLH, as a control antigen, were loaded onto the DCs. The final vaccine product consisting of Tn-100mer-MUC1 and KLH loaded DCs mixed 10:1 was cryopreserved and tested before release and administration to patients. Patients were treated with 3 vaccine injections every two weeks administered intradermally (i.d.) and intranodally (i.n.) to a single inguinal node for the first dose only. Booster i.d. vaccinations were given 6 and 12 months following the first dose in patients showing stable disease. Each dose consisted of the administration of a total of 1.2 × 107 DCs. Toxicity and biologic effects of the vaccine were evaluated by physical, imaging and clinical chemistry examinations at regular intervals. PSA doubling times were determined using the Memorial Sloan-Kettering Cancer Center PSA doubling time calculator. Results: The vaccine was safe; there were no serious vaccine-related adverse events. Toxicity was limited to grade 1 and 2 injection site reactions. Four of 7 patients treated were withdrawn after 6 months because of radiologic progression or elevated PSA. Three patients showed stable disease and received all five vaccinations. Our primary endpoint, reduction in PSA, was not achieved. However, the rate of PSA rise decreased in 6 of 7 patients. Overall the PSA doubling time increased from a median of 2.9 months prior to treatment to 7.5 months during vaccination. Conclusions: These results suggest that the DC-Tn-MUC1 vaccination is safe and induces a biological response reflected by an increase in PSA doubling time in most patients. These early results are encouraging and warrant further testing in a larger number of patients. This study was supported by CANVAC with funds from the Networks of Centres of Excellence of Canada. Citation Format: Pierre Major, Louis Lacombe, Yves Fradet, Ronan Foley, Elizabeth Scheid, Alain Bergeron, Som Mukherjee, Olivera J. Finn, Jean Gariepy, Rafick P. Sekaly, Sebastien Hotte, Sheila Chou. A phase I/II clinical trial of a MUC1-glycopeptide dendritic cell vaccine in castrate-resistant nonmetastatic prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A16.
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».