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Clinical Trials |
Departments of Tumor Immunology [I. J. M. d. V., N. M. S., L. P. H. E., R. T., G. J. A., C. G. F.], Medical Oncology [W. J. L., C. J. A. P.], Pathology [D. J. R.], Dermatology [M-J. P. G.], and Hematology [S. C.], University Medical Center St. Radboud Nijmegen and Nijmegen Center for Molecular Life Sciences, Nijmegen, the Netherlands, and Third Department of Medicine, Hematology and Oncology, Johannes Gutenberg-University of Mainz, Mainz, Germany [C. M. B.]
ABSTRACT
Purpose: We have investigated the capacity of immature and mature monocyte-derived DCs pulsed with melanoma-associated peptides (gp100 and tyrosinase) to induce a primary cytotoxic T-lymphocyte response in vivo.
Experimental Design: Advanced HLA-A2.1+ melanoma patients were vaccinated with peptide- and keyhole limpet hemocyanin (KLH)-pulsed DCs, either immature (9 patients) or matured by monocyte-conditioned medium/tumor necrosis factor 
/prostaglandin E2 (10 patients).
Results: All patients vaccinated with mature DCs showed a pronounced proliferative T-cell and humoral response against KLH. By contrast, KLH responses were absent in most of the patients vaccinated with immature DCs. Delayed-type hypersensitivity (DTH) reactions against antigen-pulsed DCs were only observed in patients vaccinated with mature DCs and not in patients vaccinated with immature DCs. MHC-peptide tetramer staining of DTH-derived T cells revealed the presence of specific T cells recognizing the melanoma-associated peptides in 1 patient. In a second patient, DTH-derived T cells showed specific lysis of tumor cells expressing the antigens used for DC pulsing. Only patients vaccinated with mature DCs showed objective clinical responses. Interestingly, both patients with long-term progression-free survival (22 and >40 months) were both vaccinated with mature DCs and demonstrated antigen-specific T-cell reactivity of DTH-derived T cells.
Conclusions: We conclude that mature DC are superior to immature DC in the induction of immunological responses in melanoma patients, which may translate into improved clinical results.
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