Samenvatting
Dendritic cell based immunotherapy for HIV is safe and immunogenic: results of a phase I/II clinical trial
B. De Keersmaecker1, A.L. de Goede2,3, S.D. Allard1,4, M.E. van der Ende5, P. Lacor4, C.A. van Baalen2, K. Thielemans1, A.D.M.E. Osterhaus2, J.L. Aerts1, R.A. Gruters2
Departments of 1Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Belgium, 2Virology, 3Hospital Pharmacy and 5Internal Medicine II, Rotterdam, the Netherlands, 4Internal Medicine and Infectious Diseases, Universitair Ziekenhuis Brussel, Belgium.
A multicenter non randomized phase I/II clinical immunotherapy trial in HIV-1 infected subjects was performed to evaluate safety and immunogenicity.
Seventeen HIV-1 infected subjects received four monthly vaccinations of autologous dendritic cells (DC) electroporated with mRNA encoding the early antigens Tat, Rev and Nef of HIV-1 consensus subtype B. Treatment was safe as no serious adverse events were reported. Effector T-cell responses were assessed by a standard IFN-? ELISpot during overnight stimulation of PBMC with overlapping peptides (peptide-ELISpot). For additional assays, PBMC were cocultured with antigen electroporated DC: IFN-? production was tested in an overnight ELISPOT assay (DC-ELISpot) and T-cell proliferation was determined in a one week CFSE assay. Results of immunemonitoring vary with the assay used. For detection of effector T-cell responses, the DC-ELISpot assay is more sensitive than the standard peptide-ELISpot. For the majority of subjects, responses against more than one of the antigens could be detected.
Antiretroviral therapy (cART) was interrupted after the immunotherapy to evaluate its effect on the course of infection. CD4+ T-cell counts declined after cART interruption in most subjects, similar to non-vaccinated historical controls. Within the same subject, plasma viral RNA levels (PVL) set-point after therapy interruption was >0.5log below pre-cART. 48 and 96 weeks after interrupting cART, 13 and 6 subjects remained off-cART, respectively. To date, the median time off-cART is 94 (28-146).
We studied viral evolution from plasma before and after immunotherapy and found limited sequence variation, with anecdotal examples of virus escape from immune pressure.
Results from this phase I/II autologous DC immunotherapy trial demonstrate that this treatment is safe and results in partial control of viral load. It induces/enhances immune responses to vaccine antigens, with limited effect on chronic HIV infection.
B. De Keersmaecker1, A.L. de Goede2,3, S.D. Allard1,4, M.E. van der Ende5, P. Lacor4, C.A. van Baalen2, K. Thielemans1, A.D.M.E. Osterhaus2, J.L. Aerts1, R.A. Gruters2
Departments of 1Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Belgium, 2Virology, 3Hospital Pharmacy and 5Internal Medicine II, Rotterdam, the Netherlands, 4Internal Medicine and Infectious Diseases, Universitair Ziekenhuis Brussel, Belgium.
A multicenter non randomized phase I/II clinical immunotherapy trial in HIV-1 infected subjects was performed to evaluate safety and immunogenicity.
Seventeen HIV-1 infected subjects received four monthly vaccinations of autologous dendritic cells (DC) electroporated with mRNA encoding the early antigens Tat, Rev and Nef of HIV-1 consensus subtype B. Treatment was safe as no serious adverse events were reported. Effector T-cell responses were assessed by a standard IFN-? ELISpot during overnight stimulation of PBMC with overlapping peptides (peptide-ELISpot). For additional assays, PBMC were cocultured with antigen electroporated DC: IFN-? production was tested in an overnight ELISPOT assay (DC-ELISpot) and T-cell proliferation was determined in a one week CFSE assay. Results of immunemonitoring vary with the assay used. For detection of effector T-cell responses, the DC-ELISpot assay is more sensitive than the standard peptide-ELISpot. For the majority of subjects, responses against more than one of the antigens could be detected.
Antiretroviral therapy (cART) was interrupted after the immunotherapy to evaluate its effect on the course of infection. CD4+ T-cell counts declined after cART interruption in most subjects, similar to non-vaccinated historical controls. Within the same subject, plasma viral RNA levels (PVL) set-point after therapy interruption was >0.5log below pre-cART. 48 and 96 weeks after interrupting cART, 13 and 6 subjects remained off-cART, respectively. To date, the median time off-cART is 94 (28-146).
We studied viral evolution from plasma before and after immunotherapy and found limited sequence variation, with anecdotal examples of virus escape from immune pressure.
Results from this phase I/II autologous DC immunotherapy trial demonstrate that this treatment is safe and results in partial control of viral load. It induces/enhances immune responses to vaccine antigens, with limited effect on chronic HIV infection.
| Originele taal-2 | English |
|---|---|
| Titel | Unknown |
| Status | Published - 2010 |