TY - JOUR
T1 - Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide
T2 - results from a phase II trial
AU - Ellebaek, Eva
AU - Engell-Noerregaard, Lotte
AU - Iversen, Trine Zeeberg
AU - Moerch Froesig, Thomas
AU - Munir, Shamaila
AU - Hadrup, Sine Reker
AU - Andersen, Mads Hald
AU - Svane, Inge Marie
PY - 2012/10
Y1 - 2012/10
N2 - Dendritic cells (DC) are the most potent antigen presenting cells and have proven eVective in stimulation of speciWc immune responses in vivo. Competing immune inhibition could limit the clinical eYcacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibitor have been added to a DC vaccine with the intend to dampen immunosuppressive mechanisms. Twenty-eight patients with progressive metastatic melanoma were treated with autologous DCs pulsed with survivin, hTERT, and p53-derived peptides (HLA-A2+) or tumor lysate (HLA-A2-). Concomitantly the patients were treated with IL-2, Cyclophosphamide, and Celecoxib. The treatment was safe and tolerable. Sixteen patients (57 %) achieved stable disease (SD) at 1st evaluation and 8 patients had prolonged SD (7-13.7 months). The median OS was 9.4 months. Patients with SD had an OS of 10.5 months while patients with progressive disease (PD) had an OS of 6.0 months (p = 0.048) even though there were no diVerences in prognostic factors between the two groups. Despite the use of metronomic Cyclophosphamide, regulatory T cells did not decrease during treatment. Indirect IFN-α ELISPOT assays showed a general increase in immune responses from baseline to the time of 4th vaccination. Induction of antigen-speciWc immune responses was seen in 9 out of 15 screened HLA-A2 + patients. In conclusion, the number of patients obtaining SD more than doubled and 6-month survival signiWcantly increased compared to a previous trial without Cyclophosphamide and Celecoxib. A general increase in immune responses against the tested peptides was observed.
AB - Dendritic cells (DC) are the most potent antigen presenting cells and have proven eVective in stimulation of speciWc immune responses in vivo. Competing immune inhibition could limit the clinical eYcacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibitor have been added to a DC vaccine with the intend to dampen immunosuppressive mechanisms. Twenty-eight patients with progressive metastatic melanoma were treated with autologous DCs pulsed with survivin, hTERT, and p53-derived peptides (HLA-A2+) or tumor lysate (HLA-A2-). Concomitantly the patients were treated with IL-2, Cyclophosphamide, and Celecoxib. The treatment was safe and tolerable. Sixteen patients (57 %) achieved stable disease (SD) at 1st evaluation and 8 patients had prolonged SD (7-13.7 months). The median OS was 9.4 months. Patients with SD had an OS of 10.5 months while patients with progressive disease (PD) had an OS of 6.0 months (p = 0.048) even though there were no diVerences in prognostic factors between the two groups. Despite the use of metronomic Cyclophosphamide, regulatory T cells did not decrease during treatment. Indirect IFN-α ELISPOT assays showed a general increase in immune responses from baseline to the time of 4th vaccination. Induction of antigen-speciWc immune responses was seen in 9 out of 15 screened HLA-A2 + patients. In conclusion, the number of patients obtaining SD more than doubled and 6-month survival signiWcantly increased compared to a previous trial without Cyclophosphamide and Celecoxib. A general increase in immune responses against the tested peptides was observed.
U2 - 10.1007/s00262-012-1242-4
DO - 10.1007/s00262-012-1242-4
M3 - Journal article
SN - 0340-7004
VL - 61
SP - 1791
EP - 1804
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 10
ER -
