The feasibility and clinical effects of dendritic cell-based immunotherapy targeting synthesized peptides for recurrent ovarian cancer

Abstract

Background: Despite the increased rate of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Dendritic cell (DC)-based immunotherapy has been developed as a novel strategy for generating antitumor immunity as part of cancer treatments. The present study aimed to assess the feasibility and clinical effects of DC therapy for recurrent ovarian cancer (ROC).

Methods: This retrospective study included 56 ROC patients who initially received standard chemotherapy followed by DC-based immunotherapy targeting synthesized peptides at 2 institutions between March 2007 and August 2013. The adverse events (AEs) and clinical responses were examined.

Results: No serious treatment-related AEs were observed. Seventy one percent of the enrolled patients developed an immunologic response. The median survival time (MST) from ROC diagnosis was 30.4 months, and that from the first vaccination was 14.5 months. Albumin levels of ≥4.0 g/dL and lactate dehydrogenase levels of <200 IU/L before vaccination were identified as significant independent factors by multivariate Cox proportional hazard analysis. The MST from the first vaccination in patients with albumin levels of ≥4.0 and <4.0 g/dL were 19.9 and 11.6 months, respectively. The corresponding disease control rates were 36% and 15%, respectively.

Conclusions: Our results demonstrated the feasibility and potential clinical effectiveness of DC-based immunotherapy for ROC patients. Additionally, a good nutritional status might be an important factor for further clinical effects.

Figure 1

Frequencies of CD4+ T cells, CD8⁺T cells, and natural killer cells in patients before and after dendritic cell-based immunotherapy targeting synthesized peptides for recurrent ovarian cancer.(A) Data on frequencies of CD4+ T cells (n = 31), (B) CD8⁺ T cells (n = 31), and (C) natural killer cells (n = 31) are expressed as a percentage of peripheral blood mononuclear cells.

Figure 2

Frequency of Wilms tumor (WT) 1-specific cytotoxic T lymphocytes (CTLs) in patients before and after therapy. WT1-specific CTLs were detected using WT1 tetramers in 17 patients. Data are expressed as a percentage of peripheral blood mononuclear cells.

Figure 3

Kaplan-Meier survival curves for the patients receiving dendritic cells-based vaccination. (Left) Survival curve from diagnosis (dotted line) and from the first vaccination (solid line). (Right) Comparison of the overall survival rates according to albumin levels (≥4.0 g/dL [solid line] and <4.0 g/dL [dotted line]).