期刊
ONCOIMMUNOLOGY
卷 5, 期 4, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2015.1071008
关键词
cancer vaccine; exosomes; immunotherapy; NSCLC; NK cell; phase II trial
资金
- Association de Recherche contre le Cancer (ARC) [SL220100601336]
- Institut National du Cancer (INCa
- Program Hospitalier de Recherche Clinique (PHRC))
- SIRIC-SOCRATE (INCa-DGOS-INSERM) [6043]
- Agence Nationale de Recherche [ANR-10-IBHU-0001]
- Fondation Gustave Roussy [PRI-2010-05]
- Deutsche Forschungsgemeinschaft [KFO286]
- ARC
- Assistance Publique Hopitaux de Paris (APHP)
- Gustave Roussy Cancer Campus
- NATIONAL CANCER INSTITUTE [P30CA016359] Funding Source: NIH RePORTER
Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN--free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN--Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN--Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN--Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN--Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC.
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