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• W2570298433 abstract "Intratumoral (IT) infiltration by activated immune effector cells is associated with a significantly better prognosis, however, tumor-associated immune suppression commonly occurs in non-small cell lung cancer (NSCLC). CD8+ T cell or dendritic cell (DC) infiltration is an independent favorable prognostic indicator. CCL21 is a lymphoid chemokine that chemo attracts both lymphocytes and DC. Our aim was to investigate anti-tumor specific systemic immune responses and tumor-infiltrating CD8+ T cells (CD8+ TIL) in NSCLC patients in response to in situ vaccination via IT administration of autologous DC transduced with a replication-deficient adenoviral (Ad) vector expressing the secondary lymphoid chemokine (SLC/CCL21) gene. Here, we conducted a phase I trial and evaluated safety and immune responses following in situ vaccination. Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 x 106, 5 x 106, 1 x 107, or 3 x 107 dendritic cells/injection) by CT- or bronchoscopic-guided IT injection (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFN-γ in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by immunohistochemistry (IHC). Twenty-five percent (4/16) of patients had stable disease at day 56 follow-up by RECIST criteria. Median survival was 3.9 months. Four possible vaccine-related grade 1 adverse events (AE) occurred in 3 patients with no clear association to dose or schedule; the AE included flu-like symptoms, blood-tinged sputum after each injection, nausea, and fatigue. ELISPOT assays revealed 38% (6/16) of 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 intratumoral CD8+ T cells following vaccination showed significantly increased PD-L1 mRNA expression (p=0.02). Intratumoral vaccination with Ad-CCL21-DC was well-tolerated and resulted in 1) induction of systemic tumor antigen-specific immune responses and 2) enhanced tumor CD8+ T cell infiltration. DC-CCL21 in situ vaccination may be a promising approach to induce tumor CD8+ T cell infiltration in combination with checkpoint inhibitor therapy." @default.
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• W2570298433 date "2017-01-01" @default.
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• W2570298433 title "MA09.07 Phase I Trial of in situ Vaccination with CCL21 Gene-Modified DC Induces Specific Systemic Immune Response and Tumor Infiltrating CD8 + T Cells" @default.
• W2570298433 doi "https://doi.org/10.1016/j.jtho.2016.11.448" @default.
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