期刊
CLINICAL CANCER RESEARCH
卷 23, 期 16, 页码 4556-4568出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-16-2821
关键词
-
类别
资金
- Thoracic Surgery Foundation Research Education (TSFRE) grant [NIH/NCIK23 CA131577]
- NIH [NCIL30 CA142223,, NCI5 K12 CA076905, NCI1 P50 CA090388, NCIR21 CA105705, NCATS UL1-TR001881]
- VA Clinical [Merit1I01CX000345-01]
Purpose: A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following in situ vaccination (ClinicalTrials. gov: NCT01574222). Experimental Design: Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 +/- 106, 5 +/- 106, 1 +/- 107, or 3 +/- 107 DCs/injection) by CT-or bronchoscopic-guided intratumoral injections (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFNg in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by IHC and for PD-L1 expression by IHC and realtime PCR (RT-PCR). Results: Twenty-five percent (4/16) of patients had stable disease at day 56. Median survival was 3.9 months. ELISPOT assays revealed 6 of 16 patients had systemic responses against tumor-associated antigens (TAA). Tumor CD8+ T-cell infiltration was induced in 54% of subjects (7/13; 3.4-fold average increase in the number of CD8+ T cells per mm2). Patients with increased CD8+ T cells following vaccination showed significantly increased PD-L1 mRNA expression. Conclusions: Intratumoral vaccination with Ad-CCL21DC resulted in (i) induction of systemic tumor antigenspecific immune responses; (ii) enhanced tumor CD8+ T-cell infiltration; and (iii) increased tumor PD-L1 expression. Future studies will evaluate the role of combination therapies with PD-1/PD-L1 checkpoint inhibition combined with DC-CCL21 in situ vaccination. (C) 2017 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据