AUTOLOGOUS DENDRITIC CELLS DERIVED FROM CD34(-PRESENTING CELLS IN THEINDUCTION OF MELAN-A() PROGENITORS AND FROM MONOCYTES ARE NOT FUNCTIONALLY EQUIVALENT ANTIGEN)MART-1(27-35)-SPECIFIC CTLS FROM PERIPHERAL-BLOOD LYMPHOCYTES OF MELANOMA PATIENTS WITH LOW-FREQUENCY OF CTL PRECURSORS/

Peptide presentation by autologous dendritic cells (DCs) is a new tool to activate tumor antigen-specific T cells in melanoma patients, Howe ver, it is not known whether autologous DCs, differentiated by tno of the most efficient protocols (from CD34(+) progenitors or from monocyt es), are equally effective as professional antigen-presenting cells (A PCs) when the patients have a low frequency of peptide-specific precur sors, To this end, a limiting dilution assay was applied to evaluate t he frequency of antigen-specific CTL precursors (CTLps) in peripheral blood of HLA-A0201(+) melanoma patients, Then, from two melanoma pati ents showing low frequency of CTLps to melanoma antigen-A/melanoma ant igen recognized by T cell (Melan-A/Mart-1)(27-35) peptide, autologous DCs were differentiated from granulocyte colony-stimulating factor-mob ilized CD34(+) progenitors or from monocytes. CD34(+)- and monocyte-de rived DCs were characterized by a similar proportion of CD1a(+) cells expressing HLA class II antigens and CD54, CD80, and CD86 molecules, B oth types of DC presented Melan-A/Mart-1(27-35) and tyrosinase(369-377 ) peptides to melanoma-specific CTL clones and were equally effective as peptide-pulsed APCs in the activation of influenza A matrix(58-66)- specific CTLs from high-frequency precursors (1294/10(6) and 1789/10(6 ) lymphocytes in the two patients), However, efficient activation of M elan-A/Mart-1(27-35)- specific CTLs from low-frequency precursors (158 /10(6) and 77/10(6) lymphocytes) of the two patients was markedly depe ndent on the use of peptide-loaded CD34(+)-derived DCs, These results suggest that CD34(+)- and monocyte-derived DCs are not functionally eq uivalent APCs for the activation of low-frequency peptide-specific CTL ps.