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

Content Provider	Springer Nature : BioMed Central
Author	de Almeida Baptista, Marcella Vassão da Silva, Laís Teodoro Samer, Sadia Oshiro, Telma Miyuki Shytaj, Iart Luca Giron, Leila B. Pena, Nathalia Mantovani Cruz, Nicolly Gosuen, Gisele Cristina Ferreira, Paulo Roberto Abrão Cunha-Neto, Edécio Galinskas, Juliana Dias, Danilo Sucupira, Maria Cecilia Araripe de Almeida-Neto, Cesar Salomão, Reinaldo da Silva Duarte, Alberto José Janini, Luís Mário Hunter, James R. Savarino, Andrea Juliano, Maria Aparecida Diaz, Ricardo Sobhie
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-α 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-γ) production were measured in CD4+ and CD8+ T-cells. Results The protocol of ex-vivo treatment with IFN-α 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-γ 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. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829 , posted November 11th, 2016)
Related Links	https://aidsrestherapy.biomedcentral.com/counter/pdf/10.1186/s12981-021-00426-z.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
ISSN	17426405
DOI	10.1186/s12981-021-00426-z
Journal	AIDS Research and Therapy
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2022-01-12
Access Restriction	Open
Subject Keyword	Infectious Diseases Virology Dendritic-cell therapy HIV GAG HLA Haplotypes HIV cure research Precision medicine
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Virology Pharmacology (medical)
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.4/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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