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Adenoviral Vector Transduction of Dendritic Cells is Inhibited by Plasma from Cancer Patients

ABSTRACT: Background: Pooled AB serum is often used as a media supplement for cell culture but it has the potential to transmit infectious diseases. To avoid this risk, we used autologous plasma as a media supplement for manufacturing dendritic cells (DCs) for cancer immunotherapy. We noticed inconsistences in the DCs and investigated its nature and cause. Methods: adHER2/neu DCs for 21 patients were manufactured from autologous peripheral blood monocytes which were treated with G-CSF and IL-4 for 3 days, transduced with Ad5f35HER2ECTM and then treated with lipopolysaccharide and IFN- for one day. The cells were cultured in RPMI-1640 supplemented with either 10% heat inactivated autologous or AB plasma. Results: Twenty-eight adHER2/neu DCs were manufactured for 21 patients using autologous plasma and 68 were manufactured for 20 of those patients using AB plasma. The expression of HER2/neu was less for DCs manufactured with autologous plasma (70.3±33.3% vs 86.1±22.8%, p<0.01). Manufacturing adHER2/neu DCs using monocytes from 3 healthy subjects and plasma from one patient with low HER2/neu expression (18%) resulted in low HER2/neu expression by all three DCs (13%, 16% and 23%). Analysis of the levels of 1322 proteins in 8 plasma samples associated with low HER2/neu expression and in 12 associated with high HER2/neu expression revealed that the levels of 14 predicted HER2/neu transduction efficiency. Conclusion: The manufacture of adHER2/neu DC using autologous plasma as a media supplement resulted in inconsistent HER2/neu expression. It is likely that variability in the levels of multiple proteins in autologous plasma contributed to low HER2/neu expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE108225 | GEO | 2018/12/17

REPOSITORIES: GEO

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