Showing papers by "Laurent Poirot published in 2014"
Patent•
01 Apr 2014
TL;DR: In this article, RNA-guided endonucleases, in particular Cas9/CRISPR system, were used to specifically target a selection of key genes in T-cells for immunotherapy.
Abstract: The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.
179 citations
Patent•
13 May 2014
TL;DR: The authors used rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells.
Abstract: The present invention relates to methods for developing engineered T-cells for immunotherapy and more specifically to methods for modifying T-cells by inactivating at immune checkpoint genes, preferably at least two selected from different pathways, to increase T-cell immune activity. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to highly efficient adoptive immunotherapy strategies for treating cancer and viral infections.
99 citations
Patent•
13 May 2014
TL;DR: This paper used rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells.
Abstract: The present invention relates to methods for developing engineered T-cells for immunotherapy that are non-alloreactive. The present invention relates to methods for modifying T-cells by inactivating both genes encoding T-cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
55 citations
Patent•
19 Dec 2014
TL;DR: In this article, a method to engineer an immune cell for immunotherapy using chimeric antigen receptors (CARs) was described. But the method was not applied to T-cells, which were used in cancer treatments.
Abstract: The present invention relates to a method to engineer immune cell for immunotherapy. In particular said immune cells are engineered with chimeric antigen receptors, which be activated by the combination of hypoxia and ligand extracellular binding as input signals. The invention also relates to new designed chimeric antigen receptors which are able to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties and the hypoxia condition. The present invention also relates to cells obtained by the present method, in particular T-cells, comprising said chimeric antigen receptors for use in cancer treatments.
44 citations
TL;DR: The ability of UCART19 cells to engraft into an orthotopic human CD19+ lymphoma xenograft immunodeficient mouse model and the effectiveness of the rituximab-induced depletion mechanism of RQR8+ cells was shown in an immunocompetent mouse model.
10 citations
TL;DR: Heterologous expression of pre-TCRα represents a promising technology for use in the manufacturing of TCR-deficient T-cells for adoptive immunotherapy applications and could be made widely available if adapted to the use of allogeneic T- cells.
Abstract: Chimeric antigen receptor technology offers a highly effective means for increasing the anti-tumor effects of autologous adoptive T-cell immunotherapy, and could be made widely available if adapted to the use of allogeneic T-cells. Although gene-editing technology can be used to remove the alloreactive potential of third party T-cells through destruction of either the α or β T-cell receptor (TCR) subunit genes, this approach results in the associated loss of surface expression of the CD3 complex. This is nonetheless problematic as it results in the lack of an important trophic signal normally mediated by the CD3 complex at the cell surface, potentially compromising T-cell survival in vivo, and eliminating the potential to expand TCR-knockout cells using stimulatory anti-CD3 antibodies. Here, we show that pre-TCRα, a TCRα surrogate that pairs with TCRβ chains to signal proper TCRβ folding during T-cell development, can be expressed in TCRα knockout mature T-cells to support CD3 expression at the cell surface. Cells expressing pre-TCR/CD3 complexes can be activated and expanded using standard CD3/CD28 T-cell activation protocols. Thus, heterologous expression of pre-TCRα represents a promising technology for use in the manufacturing of TCR-deficient T-cells for adoptive immunotherapy applications.
5 citations
TL;DR: The results provide the proof of concept for the general applicability of this approach as a platform for large-scale GMP–compliant manufacturing of allogeneic, off-the-shelf, non-alloreactive, frozen CAR T-cells.
4 citations
Patent•
01 Apr 2014
TL;DR: In this paper, a procede implique l'utilisation d'endonuclease guidees par l'ARN, en particulier le systeme Cas9/CRISPR, for cibler specifiquement une selection de genes essentiels dans les cellules T manipulees, de preference non alloreactives for l'immunotherapie.
Abstract: La presente invention concerne des procedes de developpement de cellules T genetiquement manipulees, de preference non alloreactives pour l'immunotherapie. Ce procede implique l'utilisation d'endonuclease guidees par l'ARN, en particulier le systeme Cas9/CRISPR, pour cibler specifiquement une selection de genes essentiels dans les cellules T. Les cellules T manipulees sont egalement destinees a exprimer des recepteurs d'antigene chimeriques (RAC) afin de rediriger leur activite immunitaire vers des cellules malignes ou infectees. L'invention ouvre la voie a des strategies d'immunotherapie adoptive standard et accessibles employant des cellules T pour le traitement du cancer et d'infections virales.