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Impact of chemotherapy (CT) on ex-vivo generation of dendritic cells (DCs) in advanced breast cancer (ABC) patients (pts).

2583 Background Among the several problems in planning and carrying out clinical trials with ex-vivo-generated, tumor antigen-loaded DCs for solid tumors, the pts selection, the optimal time to take blood for generating DCs and the impact on them of number and types of previous CT could also play a role. To date, high quantity of DCs can be generated after high-dose CT plus G-CSF in both BC and NHL pts. We investigated the DC yield obtainable from ABC pts in objective response after a SD, taxane-based CT program, considering these patients potentially candidate to DC-based vaccination programs. Patients and Methods Sixteen pts, aged 56 (range 43- 65), were studied 1 to 3 month after an objective response was obtained with a 1st-line CT (Epirubicin+Docetaxel combination at standard dosages, without the scheduled utilization of G-CSF) for their metastatic disease. DCs were generated from 25 ml of blood and following the standard procedure; the monocyte selection was performed with anti-CD14 microbeads (Miltenyi), followed by an immunomagnetic separation (MiniMacs, Miltenyi). DCs were analyzed for HLA-DR, CD14, and CD1a expression. Eight normal donors (NDs) were used as control and all the experiments were performed in duplicate. Results The % of DCs yielded from the same total number of monocytes was significant lower in pts compared with controls (34 vs 14, p=.00004). Irrespectively to the use of G-CSF rescue, in 3/16 pts, we were not able to generate DCs. In all pts, DCs showed very high expression of HLA-DR (> 90%) and CD1a (20-40%), demostrating a pure and immature phenotype. Conclusions Even though we were able to obtain DCs from the majority of the studied cases, a significantly lower % of DCs was generated from ABC pts with respect to the NDs. This indicate that besides clinical and biological characteristics, a potentially negative effect of the currently employed CT drugs on the phenomenon of ex vivo generation of DCs has to be taken into account when clinical trials are planned. No significant financial relationships to disclose.