Production of engineered dendritic cells and uses thereof

A technology of dendritic cells and precursor cells, applied in the direction of genetically modified cells, animal cells, vertebrate cells, etc., can solve the problems of mediating grafts, Treg instability, rejection, etc.

Pending Publication Date: 2021-04-02
フォンダツィオーネテレトン +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] - the possibility that infused Tregs are unstable under intense inflammatory conditions in vivo and adopt pathogenic effector T phenotypes and functions, thereby potentially mediating graft rejection;

Method used

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  • Production of engineered dendritic cells and uses thereof
  • Production of engineered dendritic cells and uses thereof
  • Production of engineered dendritic cells and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0451] LV-mediated gene transfer for transfer-specific Ag-derived peptides plus target sequences of miR155 and miR146a, known regulators of DC maturation (DC-Ag.miRNA), with IL-10 (DC-IL-10 / Ag) or IDO (DC-IDO / Ag), alternative strategies were developed to generate tolerogenic DC (tolLV DC) or ( figure 1 ). To determine the mode of action of tolLV-DC, the inventors used ovalbumin (OVA) as a model Ag. Generative encoding and OVA 315-353 fused Ii LVs containing OTII CD4 that can be transgenic by TCR + OVA recognized by T cells 323-339 , and this LV was used to transduce bone marrow (BM) cells during DC differentiation. LV.liOVA 315-353 .miR155T.miR146aT, LV.IL-10.IiOVA 315-353 , LV.IDO.IiOVA 315-353 , and the control LV.IiOVA 315-353 Used to obtain the following: DC-OVA, DC-OVA.miRNA, DC-IL-10 / OVA, DC-IDO / OVA. LV-DC is CD11c + and express CD80, CD86 and MHC class II at the same level as untransduced DC, ( figure 2 ). .DC-OVA promotes OTIICD4 + Proliferation of T cel...

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Abstract

The present disclosure relates to a genetically modified dendritic cell or precursor thereof expressing at least one antigen-derived peptide and at least one immuno-modulatory molecule, its medical use and method of preparation. The invention also relates to an in vitro method to produce IL-10-producing CD49b+LAG-3+ Tr1 cells or antigen-specific FOXP3+ T cells and relative medical uses and pharmaceutical compositions.

Description

technical field [0001] The present disclosure relates to genetically modified dendritic cells or precursors thereof expressing at least one antigen-derived peptide and at least one immunomodulatory molecule, their medical uses and methods of making. The present invention also relates to the production of CD49b that produces IL-10 + LAG-3+Tr1 cells or antigen-specific FOXP3 + In vitro modalities of T cells, and related medical uses and pharmaceutical compositions. Background technique [0002] Identification of novel approaches aimed at selectively controlling antigen (Ag)-specific pathogenic T-cell responses and promoting / restoring tolerance in T-cell-mediated diseases represents an ambitious goal for the management of autoimmune diseases and organ transplantation in humans one. Consistent with this, a new type of vaccination (also known as "inverse vaccination" or "tolerogenic vaccination") aims to induce or restore an immune state in unresponsive situations, This may b...

Claims

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Application Information

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IPC IPC(8): C12N5/0783C12N5/0784A61K35/15A61K35/17A61K39/00
CPCC12N2502/1121C12N2510/00C12N5/0637C12N5/064A61K38/00A61K39/39A61K39/0008A61P37/06A61P37/08A61K39/4622A61K39/464402A61K39/4621A61K39/4644A61K39/4637A61K39/4632A61K39/4615A61K2239/26A61K39/46434A61K35/15A61K45/06C12N15/85
Inventor A·安农尼S·A·格利高里
Owner フォンダツィオーネテレトン
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