146 results about "Adoptive immunity" patented technology

The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs. Such CARs, which aim to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties, comprise separate extracellular ligand binding and signaling domains in different transmembrane polypeptides. The signaling domains are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer and viral infections.

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.

The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and / or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and / or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and / or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism. Such modified T-cell is particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer, infections and auto-immune diseases.

Cancer antigens containing mutations in an expressed gene of cancer cells from a cancer patient are identified. Sequences from cancer cells obtained using a parallel sequencing platform are selected by comparing to the patient's normal genes or to normal genes from an HLA-matched individual. Sequences are further selected by identifying an HLA supertype of the cancer patient and selecting for that HLA supertype, sequences that have a particular amino acid at the mutant position and / or corresponding wild-type position in the effected gene. Peptides containing cancer antigens (i.e., mutations—once a mutation is defined, what makes it an immunogen is its ability to induce an immune response) are optionally tested for binding to HLA antigens of the cancer patient. Peptides containing the cancer antigens are evaluated for activating T cells (e.g., helper T lymphocytes and cytotoxic T lymphocytes (CTL)) cell lines from the cancer patient or from an HLA-matched donor. The cancer antigen(s) identified for a cancer patient are used to prepare a cancer vaccine and to treat the cancer patient.

In the past, adoptive immunotherapy often failed because the transferred immune cells were inactive in vivo. This disclosure provides a method of producing immune cells that are highly active in vivo. The immune cells may be expanded in vitro in the presence of an adenosine receptor agonist or an antisense nucleic acid that downregulates expression of an adenosine receptor, for example. The immune cells may be tumor-infiltrating lymphocytes (TIL), cytotoxic T lymphocytes (CTL), natural killer (NK) cells, or lymphokine-activated killer (LAK) cells, for example. The methods described herein may be used to treat a number of diseases including cancer, infectious diseases, and immunodeficiencies.

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.

The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are designed to express both a Chimeric Antigen Receptor (CAR) directed against at least one antigen expressed at the surface of a malignant or infected cell, and a secreted inhibitor of regulatory T-cells (Treg). Preferably, such secreted inhibitor is a peptide inhibitor of forkhead / winged helix transcription factor 3 (FoxP3), a specific factor involved into the differentiation of T-cells into regulatory T-cells. The engineered T-cells of the invention direct their immune activity towards specific malignant or infected cells, while at the same time will prevent neighbouring regulatory T-cells from modulating the immune response. The invention opens the way to standard and affordable adoptive immunotherapy strategies, especially for treating or preventing cancer, and bacterial or viral infections.

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.

The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.

The invention provides for compositions, e.g., pharmaceutical compositions, comprising a T lymphocyte, or a population thereof, expressing at least one recombinant polynucleotide encoding a cytokine that enhances T lymphocyte survival during the contraction phase of an immune response. The invention further provides an isolated T lymphocyte, or population thereof, expressing at least one recombinant polynucleotide encoding the cytokine, wherein the polynucleotide comprises a non-native coding sequence encoding the cytokine. Also provided is the use of such compositions and T lymphocytes, or populations thereof, for the treatment or prevention of a medical condition e.g., cancer. A method of preparing the a T lymphocyte with enhanced T cell survival is further provided herein.

The invention discloses a preparation method of antitumor adoptive immune cells. The method comprises the following steps of: sampling and separating a single peripheral blood karyocyte; and adding a cell factor for inducting and culturing to obtain a cytokine induced kill cell (CIK), wherein the cell factor comprises CD28. In a CIK induced system, the cell factor CD28 is induced, so that the inducing effect is enhanced, and the cell proliferation multiple is increased simultaneously.

Described are recombinant immunoreceptors composed of an extracellular antigen binding domain (scFv) and a transmembrane region derived from the CD3ζ-chain and / or the FcεRIγ-chain linked to an intracellular signaling domain with cell activation properties. Moreover, nucleic acid sequences encoding said immunoreceptor, immune cells expressing said immunoreceptor as well as therapeutic uses of said immunoreceptor, e.g. adoptive immunotherapy, are described.

The invention discloses application of vitamin C in in-vitro expansion of number of effector memory T cells, and the optimal concentration for promoting in-vitro expansion is found. The method has the advantages of high safety, low cost and the like, and provides a good technical support for the wide development of adoptive immunotherapy.

The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and / or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and / or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.