摘要:
The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.
摘要:
The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.
摘要:
A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T- cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
摘要:
The present invention relates to methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive drugs. The present invention relates to methods for modifying T-cells by inactivating both genes encoding target for an immunosuppressive agent and T-cell receptor, in particular genes encoding CD52 and TCR. 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.
摘要:
The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.
摘要:
The present invention is directed to compositions and methods to increase the expression of PD-L1 and/or IDO-1 in a population of cells, the modulated cells expressing increased PD-L1 and/or IDO-1, and methods related to the immunosuppressive effects obtained by cells expressing increased PD-L1 and/or IDO-1.
摘要:
The present invention provides a method polyclonal stimulation of T cells, the method comprising contacting a population of T cells with a nanomatrix, the nanomatrix comprising a) a flexible matrix, wherein said matrix is of polymeric material; and b) attached to said polymeric flexible matrix one or more polyclonal stimulatory agents which provide activation signals to the T cells; thereby activating and inducing the T cells to proliferate; wherein the nanomatrix is 1 to 500 nm in size. At least one first and one second stimulatory agents are attached to the same or to separate flexible matrices. If the stimulatory agents are attached to separate beads, fine-tuning of nanomatrices for the stimulation of the T cells is possible.
摘要:
A composition is described that comprises a treatment effective amount of cells, of which a portion are T-cells, wherein the T-cells have been harvested from cell culture and are thereby removed from activating stimuli in the culture and the harvested T-cells are formulated for infusion by a method comprising (1) contacting the T-cells with one or more agents that ligate a cell surface moiety on at least a portion of the T-cells, (2) cross-linking the one or more agents with biodegradable nanospheres or microspheres coated with a material capable of cross-linking the one or more agents, (3) suspending the T-cells, the one or more agents and the coated biodegradable nanospheres or microspheres in an infusion medium, and (4) packaging in a suitable container, wherein the T-cells are in an activated state in the medium, wherein the one or more agents are mouse-derived monoclonal antibodies, or fragments or genetically engineered derivatives thereof, and the material coating the nanospheres or microspheres is goat or sheep anti-mouse polyclonal antibodies. Methods for the preparation of the composition are also described.
摘要:
A biodegradable device for activating T-cells and a method for differentiation of T-cells using the device are disclosed, wherein, the device comprises an universal crosslinking agent comprising a biodegradable support coated with a first material, wherein the first material is capable of crosslinking more than one array of second materials, the second materials capable of binding T-cell surface moieties to deliver a signal to the T-cells, wherein each successive array of second materials has at least one second material different from the preceding array of second materials.
摘要:
The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.