Tolerogenic Dendritic cells and other tolerogenic APCs

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The Tolerogeneric Dendritic Cells and Other Tolerogenic APCs WG and WG2 (Regulatory T- Cells) will focus on 3 scientific aspects of CTT:

1. Identification and validation of QC parameters for potency/functionality

2. Identification and validation of QC parameters for safety.

3. Tailoring of CTT in different pathological conditions.

The main tasks carried out in this WG, Tolerogenic Dendritic cells and other tolerogenic APCs are:

1. Identification and validation of quality control (QC) parameters for potency (tolerogenicity) of tolDCs

It is of outstanding interest to identify functional parameters providing information on tolerogenicity of the tolDC product in robust and fast manner (once the product is ready and before its administration to the patient). Several approaches are currently used (flow-cytometric analysis of markers, such as co-stimulatory molecules, analysis of cytokine profiles of the cellular products, functional assays, etc). However, no standardised functional parameters have been defined so far.

After a thorough analysis of literature and based on shared experiences and discussions, using computer science and ontology tools, candidate functional parameters for tolerogenicity of tolDCs will be selected and validated by the different groups for their tolDC products. Furthermore microarray or proteomic analyses and comparison of different tolDCs products will be used to find additional suitable functional parameters. Functional assays (e.g. suppression of allogeneic proliferation), will be performed to confirm the tolerogenic status of generated tolDCs. Analysis of these functional parameters will facilitate the comparison of trial outcomes by tolDC products by different groups.

In addition to the identification of functional parameters of tolerogenicity for tolDCs, the efforts by this Task will contribute to the establishment of the MoA of tolerance induction by tolDCs. This Task is open to extend its scope to other tol APCs such as Mregs.

2. Identification and validation of QC parameters for safety of tolAPCs

Besides the identification of functional parameters characterising the tolAPCs, it is also important to identify and agree on the best parameter(s) that will indicate the safety of the products. The current opinion on this will be gathered using both literature and own experience. The different parameters that will emerge from this analysis, for instance, stability of the tolAPC product and ratio between expression of inhibitory and co-stimulatory molecules, will be evaluated in several in vitro assays by all the groups involved in this WG.

The identification of the QC parameters in task 1 and 2 by the A FACTT researchers will allow interaction with diagnostic companies in order to develop new reagents/ diagnostic kits. Researchers of this WG will define recommendations for regulatory authorities in order to specify relevant monitoring aspects for approval of tolDCs and other tolAPCs.

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