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Evaluating the effect of genetically engineered human plasmacytoid dendritic cells to induce specific anti-HIV responses and kill HIV-infected cells

Projekter: ProjektForskning

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Beskrivelse

Aarhus Institute of Advanced Studies Cofund Junior fellowship ID: A7873

PI: van der Sluis RM (Time salary only) 01/10/2018 – 29/09/2021

This study will aim to determine if HSC-pDC can kill HIV-infected cells directly or indirectly via the activation of CTLs and NK cells.

Lægmandssprog

The aim of this research proposal is to evaluate the potential of using donor specific stem-cells to engineer plasmacytoid dendritic cells (pDC) and use them as cell-based therapy to treat infection with human immunodeficiency virus (HIV). The objective is to examine how pDC can induce killing of HIV infected cells through i) CD8+ T cells, ii) natural killer (NK) cells iii) antibody-dependent effector cells or iv) directly by inducing a so-called “killer DC” phenotype.
HIV infection is a global health burden with 36.7 million people infected at the end of 2016 and approximately only 53% of those individuals having access to antiretroviral therapy (ART). Although ART is successful in suppressing viral load and decreasing mortality, it needs to be taken lifelong, has side effects and is expensive. Therefore, there is an urgent need to cure HIV or strategies to induce virus remission so that ART can be stopped without viral rebound.
PDC have not been used in cell-based therapy due to the limited availability from blood and the short life span ex vivo. The laboratory of my Danish mentor, A/Prof Martin Jakobsen, has developed a cell culture system that overcomes these limitations and allows for the generation of functional pDCs from CD34+ hematopoietic stem cells (HSC). We will immunologically “educate” the pDC with various HIV components and test their capacity to induce activation and cytolytic responses of CD8+ T cells, NK cells or kill HIV-infected cells directly using various cell-based elimination assays with T cell lines and primary human CD4+ T cells.
The scope of generating HIV peptide-loaded pDCs for therapeutic vaccination has great potential and has of today not been tested. We believe this work will be a platform that leads to new frontiers of translational medicine where our pDC vaccine approach can be adapted and evaluated in other immune diseases such as systemic lupus erythematosus and psoriasis.
StatusIgangværende
Effektiv start/slut dato01/10/201830/09/2021

Aktiviteter

ID: 140884925