Day 3 Poly (I:C)-activated dendritic cells generated in CellGro for use in cancer immunotherapy trials are fully comparable to standard Day 5 DCs
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24726860
DOI
10.1016/j.imlet.2014.03.010
PII: S0165-2478(14)00056-X
Knihovny.cz E-resources
- Keywords
- Cancer immunotherapy, Dendritic cell, Fast generation, Monocyte, Vaccine,
- MeSH
- Antigen-Presenting Cells drug effects immunology metabolism MeSH
- T-Cell Antigen Receptor Specificity immunology MeSH
- Cell Differentiation drug effects immunology MeSH
- Cell Culture Techniques * MeSH
- Time Factors MeSH
- Cytokines biosynthesis MeSH
- Dendritic Cells cytology drug effects immunology metabolism MeSH
- Phagocytosis immunology MeSH
- Phenotype MeSH
- Immunophenotyping MeSH
- Immunotherapy MeSH
- Humans MeSH
- Neoplasms immunology metabolism therapy MeSH
- Poly I-C immunology pharmacology MeSH
- Cancer Vaccines immunology MeSH
- T-Lymphocyte Subsets immunology metabolism MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cytokines MeSH
- Poly I-C MeSH
- Cancer Vaccines MeSH
BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells that are capable of inducing immune responses. DC-based vaccines are normally generated using a standard 5- to 7-day protocol. To shorten the DC-based vaccine production for use in cancer immunotherapy, we have developed a fast DC protocol by comparing standard DCs (Day 5 DCs) and fast DCs (Day 3 DCs). METHODS: We tested the generation of Day 5 versus Day 3 DCs using CellGro media and subsequent activation by two activation stimuli: Poly (I:C) and LPS. We evaluated DC morphology, viability, phagocyte activity, cytokine production and ability to stimulate antigen-specific T cells. RESULTS: Day 5 and Day 3 DCs exhibited similar phagocytic capacity. Poly (I:C)-activated Day 5 DCs expressed higher levels of the costimulatory and surface molecules CD80, CD86 and HLA-DR compared to Poly (I:C)-activated Day 3 DCs. Nevertheless, LPS-activated Day 5 and Day 3 DCs were phenotypically similar. Cytokine production was generally stronger when LPS was used as the maturation stimulus, and there were no significant differences between Day 5 and Day 3 DCs. Importantly, Day 5 and Day 3 DCs were able to generate comparable numbers of antigen-specific CD8(+) T cells. The number of Tregs induced by Day 5 and Day 3 DCs was also comparable. CONCLUSION: We identified monocyte-derived DCs generated in CellGro for 3 days and activated using Poly (I:C) similarly potent in most functional aspects as DCs produced by the standard 5 day protocol. These results provide the rationale for the evaluation of faster protocols for DC generation in clinical trials.
References provided by Crossref.org
Induction of Tolerance and Immunity by Dendritic Cells: Mechanisms and Clinical Applications
Generation of T cell effectors using tumor cell-loaded dendritic cells for adoptive T cell therapy