A Pilot Clinical Trial of HIV Antigen-Pulsed Allogeneic and Autologous Dendritic Cell Therapy in HIV-Infected Patients

Abstract

A pilot study was carried out to assess the safety and antigen-presenting properties of allogeneic or autologous dendritic cells (DCs) in six HLA-A2⁺, HIV-infected patients. Allogeneic DCs obtained from the peripheral blood of HLA-identical, HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope, Gag, and Pol proteins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were monitored. One allogeneic DC recipient with a CD4⁺ T cell count of 460/mm³ showed increases in envelope-specific CTL-and lymphocyte-proliferative responses, as well as in IFN-γ and IL-2 production. Another allogeneic DC recipient with a CD4⁺ T cell count of 434/mm³ also showed an increase in HIV envelope-specific lymphocyte-proliferative responses. A recipient of autologous DCs with a CD4⁺ T cell count of 730/mm³ showed an increase in peptide-specific lymphocyte-proliferative responses after three infusions. Three other allogeneic DC recipients with CD4⁺ T cell counts <410/mm³ did not show increases in their HIV-specific immune responses. No clinically significant adverse effects 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 study period. Thus, both allogeneic and autologous DC infusions were well tolerated and in patients with normal or near normal CD4⁺ T cell counts administration of these antigen-pulsed cells enhanced the immune response to HIV. However, since no effect on viral load was observed there was no evidence that this approach provided clinical benefit.