Dendritic
cells (DCs)-based therapy has proven to
be effective in patients with malignant
lymphoma, melanoma, renal and prostate carcinoma.
The objectives of this study were to assess
the toxicity and immunological response
induced by intradermally (i.d) administration
of melanoma lysate-pulsed DCs in a clinical
phase I trial. Thirteen patients with Stage
III or IV malignant melanoma were vaccinated
i.d. four times with 3.5 to 15 x 106 DCs/dose
once every 10 days. Each vaccine was composed
of a mixture of autologous DCs pulsed with
tumor lysate from three allogeneic melanoma
cell lines in the presence of KLH as adjuvant.
DCs derived from peripheral blood mononuclear
cells (PBMCs) were morphologic, phenotypic,
and functionally characterized in vitro.
PBMC harvested before the treatment, one
week after each vaccination and one month
after the last immunization, were analyzed
using ELISPOT. |
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Twelve
patients received all four vaccines and
were examined for toxicity and/or immunological
responses. There were no grade III or IV
toxicities associated with the vaccines
or evidence of autoimmunity. After vaccination,
7 of 12 tested patients showed an increased
IFN-g production by PBMC in response to
allogeneic melanoma cell lines but not to
non-melanoma tumor controls. Four of five
HLA-A2+ PBMC from patients with anti melanoma
activity also showed specific responses
against peptides derived from melanoma associated
antigens. In vivo, DTH reactions against
melanoma cell lysate were observed in 7
of 12 tested patients. In four patients,
the disease remained stable for more than
20 months, while the disease progressed
in 8 patients. No vitiligo was observed.
This study may be one of the first experiences
in Latin America using DC based vaccines
for the treatment of cancer. More patients
and additional studies are necessary to
improve tumor rejection response.
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