A PILOT CLINICAL-TRIAL OF HIV ANTIGEN-PULSED ALLOGENEIC AND AUTOLOGOUS DENDRITIC CELL THERAPY IN HIV-INFECTED PATIENTS

A pilot study was carried out to assess the safety and antigen-present ing properties of allogeneic or autologous dendritic cells (DCs) in si x HLA-A2(+), HIV-infected patients. Allogeneic DCs obtained from the p eripheral blood of HLA-identical, HIV-seronegative siblings were pulse d with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope, Gag, and Pol prot eins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were moni tored. One allogeneic DC recipient with a CD4(+) T cell count of 460/m m(3) showed increases in envelope-specific CTL-and lymphocyte-prolifer ative responses, as well as in IFN-gamma and IL-2 production. Another allogeneic DC recipient with a CD4(+) T cell count of 434/mm(3) also s howed an increase in HIV envelope-specific lymphocyte-proliferative re sponses. A recipient of autologous DCs with a CD4(+) T cell count of 7 30/mm(3) showed an increase in peptide-specific lymphocyte-proliferati ve responses after three infusions. Three other allogeneic DC recipien ts with CD4(+) T cell counts <410/mm(3) did not show increases in thei r HIV-specific immune responses. No clinically significant adverse eff ects were noted in this study and CD4(+) T cell numbers and plasma HIV -1 RNA detected by RT-PCR of all six patients were stable during the s tudy period. Thus, both allogeneic and autologous DC infusions mere we ll tolerated and in patients with normal or near normal CD4(+) T cell counts administration of these antigen-pulsed cells enhanced the immun e response to HIV, However, since no effect on viral load was observed there was no evidence that this approach provided clinical benefit.