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Phase I Trial of Intratumoral Injection of CCL21 Gene-Modified Dendritic Cells in Lung Cancer Elicits Tumor-Specific Immune Responses and CD8 + T-cell Infiltration
Ist Teil von
Clinical cancer research, 2017-08, Vol.23 (16), p.4556-4568
Ort / Verlag
United States: American Association for Cancer Research Inc
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
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
gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following
vaccination (ClinicalTrials.gov: NCT01574222).
Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 × 10
, 5 × 10
, 1 × 10
, or 3 × 10
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 IFNγ in ELISPOT assays. Tumor biopsies were evaluated for CD8
T cells by IHC and for PD-L1 expression by IHC and real-time PCR (RT-PCR).
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 mm
). Patients with increased CD8
T cells following vaccination showed significantly increased PD-L1 mRNA expression.
Intratumoral vaccination with Ad-CCL21-DC resulted in (i) induction of systemic tumor antigen-specific 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
vaccination.
.