Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses by<i>gag</i>mRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals

Gulck, Ellen R. Van; Vanham, Guido; Heyndríckx, Leo; Coppens, Sandra; Vereecken, Katleen; Atkinson, Derek; Florence, Éric; Kint, Ilse; Berneman, Zwi; Tendeloo, Viggo Van

doi:10.1128/jvi.02080-07

Cited by 26 publications

(18 citation statements)

References 70 publications

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“…In addition, HAART-treated individuals showed a reduced expression level of PD-1 comparable with the expression found in LTNP [37,130]. We have shown in vitro a significant but limited improvement of effector function when anti-PDL1 was added, underscoring the importance of this pathway [117].…”

Section: Obstacles To Be Overcome For Effective Immunotherapymentioning

confidence: 76%

“…Moreover, non-specific immune responses were also induced when using plasmid DNA transfection of DC. In contrast, transfection with mRNA encoding antigens requires cytoplasmic penetration only and has turned out to be a very efficient method for loading DC with antigens and subsequent stimulation of HIV-specific T cells [115][116][117][118]. mRNA encoding consensus or clade-specific HIV antigens (e.g.…”

Section: Antigen Loading Strategies For DCmentioning

confidence: 94%

“…In our study, we confirmed that our cytokine-treated Mo-DC indeed increased the frequency of cells with a Treg phenotype. However, we doubt that those are also functionally active Treg, since we could not show their suppressive activity based on proliferation, blocking and depletion experiments [117].…”

Section: Obstacles To Be Overcome For Effective Immunotherapymentioning

confidence: 98%

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Role of Dendritic Cells in HIV-Immunotherapy

Gulck¹,

Tendeloo²,

Berneman³

et al. 2010

CHR

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HIV remains one of the most important deadly infections today, due to the lack of a preventive vaccine and limited access to medical care in developing countries. In developed countries, antiretroviral therapy is available, but it can not eliminate the virus, implying that life-long therapy is necessary. Therefore, it is important that other strategies such as therapeutic vaccination will be developed to control virus replication or even eliminate the virus. The major obstacles towards such a strategy are the huge variability of the virus and the profound HIV-induced immune dysfunction. In this review we focus on dendritic cell based immunotherapies against HIV. To develop an efficient immunotherapy, several elements should be taken into account such as which antigen and loading strategy to use, how to deliver the immunogen, how to optimize the interaction between antigenic peptide and T cells and avoid tolerance. Clearly, to develop an immunotherapy to complement the effect of HAART, it is not sufficient to enhance T cell responses against a consensus sequence or against the prevailing plasma virus. Broad and potent immune response are needed to suppress the entire quasispecies, including the latent reservoir, and to prevent any escape.

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Section: Obstacles To Be Overcome For Effective Immunotherapymentioning

confidence: 76%

Section: Antigen Loading Strategies For DCmentioning

confidence: 94%

Section: Obstacles To Be Overcome For Effective Immunotherapymentioning

confidence: 98%

See 1 more Smart Citation

Role of Dendritic Cells in HIV-Immunotherapy

Gulck¹,

Tendeloo²,

Berneman³

et al. 2010

CHR

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“…By contrast, using cells from pre-tumor cirrhotic patients, we were able to expand potentially tumor-reactive multifunctional T-cells in a significant minority of subjects using 15mer peptide antigens. Further optimization of the approach with techniques such as codon-optimized DNA [44], co-transfection with cytokine -encoding DNA [45–47], or co-transfection with PAMPs [48–50] could increase the frequency of tumor-reactive T-cells generatable with cell-based vaccinations. We postulate that translation of an optimized MoDC approach using HCC-related antigens in pre-tumor cirrhotic patients has the potential to prevent or delay progression to hepatocellular carcinoma in this high risk population.…”

Section: Discussionmentioning

confidence: 99%

Monocyte-derived dendritic cells from cirrhotic patients retain similar capacity for maturation/activation and antigen presentation as those from healthy subjects

Tanoue

Chang²,

Li³

et al. 2015

Cellular Immunology

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Few studies have investigated the impact of liver cirrhosis on dendritic cell function. The purpose of this study was to compare the activation and antigen-presentation capacity of monocyte-derived dendritic cells (MoDC) from cirrhotic patients (CIR) relative to healthy donors (HD). MoDC from CIR and HD were matured, phenotyped, irradiated and pulsed with 15mer peptides for two hepatocellular carcinoma-related antigens, alphafetoprotein and glypican-3, then co-cultured with autologous T-cells. Expanded T-cells were evaluated by interferon-gamma ELISPOT and intracellular staining. 15 CIR and 7 HD were studied. While CD14+ monocytes from CIR displayed enhanced M2 polarization, under MoDC-polarizing conditions, we identified no significant difference between HD and CIR in maturation-induced upregulation of co-stimulation markers. Furthermore, no significant differences were observed between CIR and HD in subsequent expansion of tumor antigen-specific IFNγ+ T-cells. Conclusion MoDCs isolated from cirrhotic individuals retain similar capacity for in vitro activation, maturation and antigen-presentation as those from healthy donors.

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“…Nucleofection of mRNA results in high expression of HIV or simian immunodeficiency virus (SIV) RNA [77]. Stimulation of T cells from HIV-seropositive individuals with autologous proviral gag mRNA-electroporated DC expands both CD4 + and CD8 + T cells with broad recognition of Gag epitopes [78,79]. However endogenous degradation of the transfected mRNA is a potential problem.…”

Section: Hiv Antigen Used In Dc-based Immunotherapymentioning

confidence: 99%

Advances in Dendritic Cell-Based Vaccines for HIV

Patham¹,

Simmons²,

Subramanya³

2011

CMC

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HIV remains one of the most important deadly infections today, due to the lack of a preventive vaccine and limited access to medical care in developing countries. In developed countries antiretroviral therapy is available but the regime is unable to eliminate the virus, implying that life-long therapy is necessary. Dendritic cells (DCs) are important mediators of cellular and humoral immune responses and hence offer a promising therapeutic vaccination strategy to attenuate disease progression. The current knowledge in DC subsets and their functional plasticity are prominent determinants in harnessing the full immunostimulatory potential of dendritic cells. Type of antigen, immunogen delivery method, optimal interaction of antigenic peptide and T cells, and avoidance of tolerogenic responses are some of the elements that need to be considered to develop an efficient immunotherapy. Novel strategies that modulate DC functions that eventually trigger a robust cellular response against a broad T cell repertoire are needed. This review focuses on current DC-based vaccine strategies for optimal induction of immune responses.

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Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses bygagmRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals

Abstract: Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (

Cited by 26 publications

References 70 publications

Role of Dendritic Cells in HIV-Immunotherapy

Role of Dendritic Cells in HIV-Immunotherapy

Monocyte-derived dendritic cells from cirrhotic patients retain similar capacity for maturation/activation and antigen presentation as those from healthy subjects

Advances in Dendritic Cell-Based Vaccines for HIV

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