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Autologous Dendritic Cells Derived from CD34⁺ Progenitors and from Monocytes Are Not Functionally Equivalent Antigen-presenting Cells in the Induction of Melan-A/Mart-1_27–35-specific CTLs from Peripheral Blood Lymphocytes of Melanoma Patients with Low Frequency of CTL Precursors¹

Divisions of Experimental Oncology D [R. M., A. A., A. M., G. P.], Medical Oncology C [M. D. N., S. S., M. B., A. M. G.], and Surgical Oncology B [F. B.], Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy

Peptide presentation by autologous dendritic cells (DCs) is a new tool to activate tumor antigen-specific T cells in melanoma patients. However, it is not known whether autologous DCs, differentiated by two of the most efficient protocols (from CD34⁺ progenitors or from monocytes), are equally effective as professional antigen-presenting cells (APCs) when the patients have a low frequency of peptide-specific precursors. To this end, a limiting dilution assay was applied to evaluate the frequency of antigen-specific CTL precursors (CTLps) in peripheral blood of HLA-A*0201⁺ melanoma patients. Then, from two melanoma patients showing low frequency of CTLps to melanoma antigen-A/melanoma antigen recognized by T cell (Melan-A/Mart-1)_27–35 peptide, autologous DCs were differentiated from granulocyte colony-stimulating factor-mobilized CD34⁺ progenitors or from monocytes. CD34⁺- and monocyte-derived DCs were characterized by a similar proportion of CD1a⁺ cells expressing HLA class II antigens and CD54, CD80, and CD86 molecules. Both 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 (1294/10⁶ and 1789/10⁶ lymphocytes in the two patients). However, efficient activation of Melan-A/Mart-1_27–35-specific CTLs from low-frequency precursors (158/10⁶ and 77/10⁶ lymphocytes) of the two patients was markedly dependent on the use of peptide-loaded CD34⁺-derived DCs. These results suggest that CD34⁺- and monocyte-derived DCs are not functionally equivalent APCs for the activation of low-frequency peptide-specific CTLps.

¹ This work was supported in part by funds from National Research Council (Rome, Italy), the Italian Association for Cancer Research (Milan, Italy), and the Italy-United States Program on Therapy of Tumors (Rome, Italy).

² To whom requests for reprints should be addressed, at Division of Experimental Oncology D, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. Phone: 39-2-2390633; Fax: 39-2-2362692; E-mail: mortarini@istitutotumori.mi.it.

Received 8/ 6/97. Accepted 10/15/97.

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