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Published on: January 6, 2014
An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational
Jitka Fucikova1,2, Michal Hensler1, Lenka Kasikova1
1Sotio Biotech, Prague, Czech Republic.
Purpose:
The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) has recently been shown to be safe and to significantly improve progression-free survival (PFS) in a randomized phase II clinical trial enrolling patients with EOC (SOV01, NCT02107937).
Patients And Methods:
We harnessed sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC to analyze (pretreatment) tumor and (pretreatment and posttreatment) peripheral blood samples from 82 patients enrolled in SOV01, with the aim of identifying immunologic biomarkers that would improve the clinical management of patients with EOC treated with DCVAC.
Results:
Although higher-than-median TMB and abundant CD8+ T-cell infiltration were associated with superior clinical benefits in patients with EOC receiving standard-of-care chemotherapy, the same did not hold true in women receiving DCVAC. Conversely, superior clinical responses to DCVAC were observed in patients with lower-than-median TMB and scarce CD8+ T-cell infiltration. Such responses were accompanied by signs of improved effector functions and tumor-specific cytotoxicity in the peripheral blood.
Conclusions:
Our findings suggest that while patients with highly infiltrated, "hot" EOCs benefit from chemotherapy, women with "cold" EOCs may instead require DC-based vaccination to jumpstart clinically relevant anticancer immune responses.
Insights
Epithelial ovarian carcinoma (EOC) patients with "cold" tumors, characterized by low tumor mutational burden and scarce CD8+ T-cells, may benefit from dendritic cell (DC)-based vaccines (DCVAC). This approach can stimulate anti-cancer immune responses in EOC patients unresponsive to standard therapies.
Area of Science:
- Immunology
- Oncology
- Vaccinology
Background:
- Immune checkpoint inhibitors (ICIs) show limited efficacy in epithelial ovarian carcinoma (EOC) due to low tumor mutational burden (TMB) and poor T-cell infiltration.
- An autologous dendritic cell (DC)-based vaccine (DCVAC) demonstrated safety and improved progression-free survival (PFS) in an EOC phase II trial (SOV01).
Purpose of the Study:
- To identify immunologic biomarkers predicting response to DCVAC in EOC patients.
- To guide the clinical management of EOC patients undergoing DCVAC therapy.
Main Methods:
- Analysis of tumor and peripheral blood samples from 82 EOC patients in the SOV01 trial.
- Utilized sequencing, flow cytometry, multispectral immunofluorescence microscopy, and IHC.
Main Results:
- Unlike chemotherapy, DCVAC efficacy in EOC was associated with lower-than-median TMB and scarce CD8+ T-cell infiltration.
- Patients responding to DCVAC showed enhanced peripheral blood effector functions and tumor-specific cytotoxicity.
- High TMB and CD8+ T-cell infiltration predicted better outcomes with chemotherapy, not DCVAC.
Conclusions:
- EOC patients with "hot" tumors (high TMB, CD8+ infiltration) may benefit more from chemotherapy.
- EOC patients with "cold" tumors (low TMB, low CD8+ infiltration) might benefit from DCVAC to initiate anti-cancer immune responses.
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