Abstract CT226: A pilot study of adoptive cell therapy with in vitro educated MART1 T cells in combination with ipilimumab for the treatment of metastatic melanoma
Notice bibliographique
Résumé
Abstract Background: The majority of ACT approaches use pre-conditioning lymphodepletion as a prerequisite for achieving clinical activity. For TIL therapy, high dose IL-2 is also required. As an alternative to the toxicity of this approach our group has developed a method for efficiently generating anti-tumor CD8+ T cells, using a novel clinical grade artificial (HLA-A*0201+, CD80+ and CD83+) antigen presenting cell (aAPC). A completed phase I clinical study (Butler 2011) demonstrated that this aAPC can in vitro-educate tumor antigen specific T cells enabling them to induce responses and establish anti-tumor memory without the use of lymphodepletion, vaccination, or cytokine injections. Detection of transferred aAPC educated MART1 T cells showed trafficking to tumor and an increased frequency of MART1 T cells with a central or effector memory phenotype. Durable responses were seen particularly in patients subsequently treated with ipilimumab. Trial design: A phase I trial of ACT with our novel in vitro educated CD8+T cells in combination with ipilimumab was designed to evaluate safety, feasibility and efficacy of this novel combination. Eligible patients must be HLA-A*0201+, ECOG 0/1, have evaluable disease which is MART1+ by IHC and have adequate organ function. Any number of previous therapies are allowed, including ipilimumab. Patients with stable brain metastases will also be eligible. Patients will undergo leukapheresis to harvest autologous PBMC and a CliniMACs will be used to isolate CD8 T cells for in vitro expansion and priming with MART1 peptide pulsed and irradiated aAPC. One infusion of CD8+ in vitro educated T cells will be given followed by ipilimumab for 4 cycles. Tumor biopsies will be performed at baseline, after 4 cycles of ipilimumab treatment, and at the time of progression. CT assessment scans will be performed at baseline, upon completion of treatment and every three months thereafter. Responses will be determined according to RECIST v1.1 and irRC. Immune correlates will be assessed by serial peripheral phlebotomy at defined time points during treatment; at baseline, prior to each treatment, at the end of all treatment, 3 monthly thereafter and at the time of progression. A target of ten patients will be recruited. As the primary aim is to assess feasibility and safety of this treatment no formal statistical power is required. We will however use Welch's t test to assess for statistically significant changes (during treatment and follow up) in MART1 T cell frequency and phenotype in two-sample comparisons and the Wilcoxon signed-rank test for paired comparisons. Citation Format: leila Khoja, Anthony M. Joshua, Lisa Wang, David Hogg, Linh Nguyen, Valentin Sotov, Vinicius Motta, Liz Scheid, Diana Gray, Nato Hirano, Marcus O. Butler. A pilot study of adoptive cell therapy with in vitro educated MART1 T cells in combination with ipilimumab for the treatment of metastatic melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT226. doi:10.1158/1538-7445.AM2015-CT226
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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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| 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 ».