An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer with Low Mutational Burden and Cold Tumors
Language English Country United States Media print
Document type Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
PubMed
35536547
DOI
10.1158/1078-0432.ccr-21-4413
PII: 696491
Knihovny.cz E-resources
- MeSH
- Dendritic Cells MeSH
- Carcinoma, Ovarian Epithelial * genetics therapy MeSH
- Humans MeSH
- Mutation MeSH
- Biomarkers, Tumor MeSH
- Ovarian Neoplasms * genetics therapy MeSH
- Cancer Vaccines * therapeutic use MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Names of Substances
- Biomarkers, Tumor MeSH
- Cancer Vaccines * MeSH
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.
Caryl and Israel Englander Institute for Precision Medicine Weill Cornell Medicine New York New York
Centre De Recherche Des Cordeliers INSERM Sorbonne Université Université De Paris Paris France
Department of Gynaecology and Obstetrics Leuven Cancer Institute UZ Leuven Leuven Belgium
Department of Radiation Oncology Weill Cornell Medicine New York New York
Equipe Labellisée Ligue Contre Le Cancer Paris France
INSERM UMRS1138 Laboratory of Integrative Cancer Immunology Cordeliers Research Center Paris France
Sandra and Edward Meyer Cancer Center Weill Cornell Medicine New York New York
References provided by Crossref.org
Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors
Trial watch: Dendritic cell (DC)-based immunotherapy for cancer
ClinicalTrials.gov
NCT02107937
