Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay.
Assessment of the chemosensitivity of dendritic cells (DC) may allow more rational development of combined chemotherapy and immunotherapy protocols. Human monocyte-derived DC generated reproducible results in the MTS (Owen's reagent) assay, which was then used to study DC survival after treatment with four different chemotherapy agents. DC preparations from three different donors were used per drug. DC were sensitive to doxorubicin (concentration range 0.1-50 microM) with variation in sensitivity between donors (IC50 244-1100 nM). The most extreme variation was seen for vinblastine (concentration range 250-0.025 microM with IC50 0.15-17.25 microM). In contrast, there was relative resistance to etoposide (concentration range 0.2-200 microM) and 5-fluorouracil (concentration range 0.7-7700 microM) with no toxicity seen until 50 microM and 770 microM respectively. The function of DC in allogeneic mixed leucocyte reactions closely paralleled results from the MTS assays. The differential sensitivity to chemotherapy agents did not appear to be due to expression of P-glycoprotein. These results suggest that etoposide or 5-fluorouracil is less likely to reduce the immunotherapeutic potential of DC and may be valuable in the design of prodrug activation therapy.
Chao
D
D
Nuffield Department of Surgery, John Radcliffe Hospital, Headington, Oxford, UK.
Bahl
P
P
Houlbrook
S
S
Hoy
L
L
Harris
A
A
Austyn
J M
JM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D015203:Reproducibility of Results
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents