mmunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical tria

Author(s):Show less -

de Almeida Baptista, Marcella Vassao ^[1] ; da Silva, Lais Teodoro ^[2] ; Samer, Sadia ^[3] ; Oshiro, Telma Miyuki ^[2] ; Shytaj, Iart Luca ^[1] ; Giron, Leila B. ^[4] ; Pena, Nathalia Mantovani ^[1] ; Cruz, Nicolly ^[1] ; Gosuen, Gisele Cristina ^[1] ; Abrao Ferreira, Paulo Roberto ^[1] ; Cunha-Neto, Edecio ^{[5, 6]} ; Galinskas, Juliana ^[1] ; Dias, Danilo ^[1] ; Araripe Sucupira, Maria Cecilia ^[1] ; de Almeida-Neto, Cesar ^{[5, 6]} ; Salomao, Reinaldo ^[1] ; da Silva Duarte, Alberto Jose ^[2] ; Janini, Luis Mario ^[1] ; Hunter, James R. ^[1] ; Savarino, Andrea ^[7] ; Juliano, Maria Aparecida ^[1] ; Diaz, Ricardo Sobhie ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Retrovirol Lab, R Pedro Toledo 669, BR-04039032 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, LIM 56, Av Dr Eneas Carvalho Aguiar 255, BR-05403000 Sao Paulo, SP - Brazil

^[3] Northwestern Univ, Dept Cell & Dev Biol, 300 E Super St, Chicago, IL 60611 - USA

^[4] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 - USA

^[5] Univ Sao Paulo, Disciplina Ciencias Med, Fac Med, Sao Paulo - Brazil

^[6] Fundacao Prosangue Hemoctr Sao Paulo, Dept Afereses, Sao Paulo - Brazil

^[7] Italian Inst Hlth, Dept Infect Dis, Viale Regina Elena 299, I-00161 Rome - Italy

• Document type: Journal article
• Source: AIDS RESEARCH AND THERAPY; v. 19, n. 1 JAN 12 2022.
• Web of Science Citations: 0

Abstract

Background: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. Methods: PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-alpha and GM-CSF. After sequencing each patient's HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients' cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-gamma) production were measured in CD4(+) and CD8(+)T-cells. Results: The protocol of ex-vivo treatment with IFN-a and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4(+) and CD8(+)T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-gamma expression was significantly increased in CD4(+) T-cells. The number of candidates that increased in vitro the cytokine levels in CD4(+) and CD8(+)T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. Conclusions: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. (AU)

• FAPESP's process: 19/17461-7 - Use of dendritic cell vaccine in association with strategies for elimination of viral reservoirs aiming at the sterilizing cure of HIV-1 infection in chronically infected persons using antiretroviral treatment
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 13/11323-5 - Multi interventional study exploring HIV-1 residual replication: a step towards HIV-1 eradication and sterilizing cure
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Regular Research Grants