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Clinical trials of DC-based immmunotherapy of HIV infected individuals

clinical study dataset

A phase I/II study of immunization of HIV infected individuals stable under HAART has been initiated which will provide us with immunological data. These patients are being vaccinated with cytokine cocktail matured DCs electroporated with mRNA encoding Tat, Rev and Nef. The cDNA’s encoding these early expressed HIV antigens have been human codon optimized and modified with lysosomal targeting sequences. Four vaccines separated by 4 weeks. Two weeks after the 4th vaccine, an analytical HAART interruption was started. So far, 17 patients have been included in this study.

Background:
The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutic strategies. One of the approaches that has gained prominence in recent years is therapeutic vaccination. We decided to assess the capacity of mature dendritic cells, derived from blood monocytes of HIV-1 infected patients, to generate functional T-cell responses. For this purpose, we constructed a chimeric mRNA encoding the proteins Tat, Rev and Nef. The TaReNef encoding information was linked to the HLA class II-targeting sequence of DC-LAMP. Broadly directed HIV-specific CD4(+) and CD8(+) cytotoxic T cells exhibiting a poly-functional cytokine secretion pattern were generated by co-culturing with autologous chimeric mRNA electroporated dendritic cells. Thus, administration of ex vivo generated dendritic cells expressing the early proteins Tat, Rev and Nef might offer a promising approach for therapeutic vaccination in HIV-1 infection.

Clinical and immunological follow-up is ongoing.





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