Abstract B51: Synergistic effects of αCTLA-4 and radiotherapy in the treatment of prostate cancer.
Notice bibliographique
Résumé
Abstract Objective: External Beam Radiation Therapy (EBRT) in combination with androgen deprivation therapy (ADT) is the standard treatment for high risk, non-metastatic prostate cancer but frequently fails to provide durable responses. It causes tumor necrosis and tumor antigen presentation to the immune system with subsequent activation of T cells, a phenomenon that is inhibited by CTLA-4. As a result, CTLA-4 blockade therapy has the potential of enhancing effector T cell responses and therefore, improving treatment effectiveness and patient outcomes. CTLA-4 blockade therapy utilizing anti-CTLA4 antibodies has been studied in patients with metastatic, castrate resistant prostate cancer with promising results. However, the role of such therapy in combination with ADT and EBRT in high-risk, non-metastatic prostate cancer is currently unknown. In this study, the safety and efficacy of CTLA-4 blockade in combination with EBRT and ADT was investigated in a syngeneic murine prostate tumor model. Materials and Methods: TRAMP-C2 prostate tumors were established in wild-type mice for 1 month prior to surgical castration. Mice were stratified into 3 groups. Group 1: Two weeks after castration, tumors were radiated with 3 doses of 10 Gy over a period of 10 days. Group 2: Mice received 3 x 10 mg/kg doses of αCTLA-4 (9H10) daily, starting 2 or 10 days after castration. Group 3: Mice received αCTLA-4 (3 x 10 mg/kg) concurrently with radiation treatment. Peripheral blood was monitored weekly for changes in T cell subsets. Tumor growth, survival, toxicity and reactivity to a H2-Db epitope of SPAS-1 were also assessed. Results: There were no αCTLA-4 treatment-related morbidity or mortalities. αCTLA-4 started at 10 days after castration, or concurrently with radiation had a longer median survival (127 days and 122.5 days, respectively) compared to mice receiving αCTLA-4 earlier (72.5 days median survival). Mice that only received castration and radiation had a median survival time of 70 days. In addition, an increase in antigen experienced CD8+ T cells was detected in mice receiving αCTLA-4 closest to or during radiation therapy. Recall assays indicated that SPAS-1 specific T cells were only detectable in αCTLA-4 treated mice. Two weeks after radiation, there was also a 2-fold increase in ICOS+ CD4+ T cells in mice that had been treated with αCTLA-4 immediately prior to radiation as compared to those that had been treated immediately after castration. Conclusions: Administration of αCTLA-4 close to, or during EBRT in combination with ADT delays tumor growth and improves survival in the TRAMP-C2 prostate cancer tumor model in part through increases in antigen specific CD8+ T cells. Future studies will further elucidate the mechanism of action of this combined therapy and pave the way for the development of clinical trials in high risk prostate cancer patients. Citation Format: Lisa DS Johnson, Wayne A. Beckham, Gordon H. Russell, Julian J. Lum, Maria T. Vlachaki. Synergistic effects of αCTLA-4 and radiotherapy in the treatment of prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B51.
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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) | 0,003 | 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 ».