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Cell Mol Immunol. 2015 Jan;12(1):87-95. doi: 10.1038/cmi.2014.40. Epub 2014 Jun 30.

Therapeutic DC vaccination with IL-2 as a consolidation therapy for ovarian cancer patients: a phase I/II trial.

Author information

1
Office of Biomedical Professors, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Department of Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
3
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korean.
4
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korean.
5
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
6
FCB-Pharmicell Co. Ltd, Seoul, Korea.

Abstract

While ovarian cancer (OvCa) responds well to surgery and conventional chemotherapy, a high recurrence rate of advanced OvCa is observed. In this phase I/II study, 10 OvCa patients with minimal residual disease were treated with autologous dendritic cells (DCs) and IL-2 to evaluate the safety and feasibility of this therapeutic strategy and to characterize the antigen-specific immune alterations induced through this treatment. Approximately 4 months after initial debulking and chemotherapy, patients received two subcutaneous doses of autologous monocyte-derived DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) at 4-week intervals. After each DC inoculation, low-dose (200 mIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. The vaccination was well tolerated. In three out of 10 patients, the inclusion status after the initial therapy showed the maintenance of complete remission (CR) after DC vaccination for 83, 80.9 and 38.2 months without disease relapse. One patient with stable disease (SD) experienced the complete disappearance of tumor after DC vaccination, and this status was maintained for 50.8 months until tumor recurrence. In two patients with partial response (PR) was not responding to DC vaccination and their disease recurred. In the three patients with disease free long-term survival, significant immune alterations were observed, including increased natural killer (NK) activity, IFN-γ-secreting T cells, immune-stimulatory cytokine secretion and reduced immune-suppressive factor secretion after DC vaccination. Thus, in patients with NED status and increased overall survival, DC vaccination induced tumor-related immunity, potentially associated with long-term clinical responses against OvCa.

PMID:
24976269
PMCID:
PMC4654372
DOI:
10.1038/cmi.2014.40
[Indexed for MEDLINE]
Free PMC Article

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