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.
Abstract:
The invention relates to cell death inducing chimeric antigen receptors (D-CAR). In particular, the present invention relates to cell death inducing chimeric antigen receptors which comprise at least one death domain in their endodomain, including cell death inducing chimeric antigen receptors comprising within their death domains modifications which attenuate the self-association and/or binding to pro-apoptotic or pro-necrotic adaptor proteins, such as FADD or TRADD. Moreover, the present invention relates to an engineered immune cell expressing at its surface a cell death inducing CAR of the present invention and, optionally, an activating chimeric antigen receptor, wherein the extracellular ligand-binding domains of the cell death inducing CAR and the activating CAR bind to different antigens. The engineered immune cell may furthermore comprise at least one edited (e.g., inactivated) gene selected from TCR genes, immune check point genes, genes involved in drug resistance, and combinations thereof.
Abstract:
The present invention relates to therapeutic cells for immunotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering prodrug-specific hypersensitive T-cell, which can be depleted in vivo by the administration of said specific prodrug in case of occurrence of a serious adverse event. The invention opens the way to safer and tunable adoptive immunotherapy strategies for treating cancer.
Abstract:
The present invention relates to therapeutic cells for immunotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering drug-specific hypersensitive T-cell, which can be depleted in vivo by the administration of said specific drug in case of occurrence of a serious adverse even. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer.
Abstract:
The present invention is in the field of a method for genome engineering based on the type II CRISPR system, particularly a method for improving specificity and reducing potential off-site. The method is based on the use of nickase architectures of Cas9 and single or multiple crRNA(s) harboring two different targets lowering the risk of producing off-site cleavage. The present invention also relates to polypeptides, polynucleotides, vectors, compositions, therapeutic applications related to the method described here.
Abstract:
The present invention relates to methods for developing engineered immune cells such as T-cells for immunotherapy that have a higher potential of persistence and/or engraftment in host organism. IN particular, this method involves an inactivation of at least one gene involved in self/non self recognition, combined with a step of contact with at least one non-endogenous immunosuppressive polypeptide. The invention allows the possibility for a standard and affordable adoptive immunotherapy, whereby the risk of GvH is reduced.
Abstract:
The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from an anti-HSP70 monoclonal antibody, conferring specific immunity against HSP70 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating in particular leukemia.
Abstract:
A single chain homing endonuclease, comprising a first variant of I-CreI having the amino acid sequence of accession number pdb 1g9y and a second variant of I-CreI variant having the amino acid sequence of accession number pdb 1g9y in a single polypeptide.
Abstract:
The present invention relates to the design of improved TALE protein fusions useful as sequence-specific genomic reagents, such as TALE-nucleases and TALE base editors, displaying higher on-target/off-target activity ratios. Its goal is to produce safer reagents to genetically modify the genomes of different types of cells, especially mammalian cells, in particular for their use in gene therapy.
Abstract:
The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.