Juno Therapeutics Gmbh

Iba Gmbh

Technische Universitaet Muenchen

Lothar Germeroth

Christian Stemberger

Dirk H Busch

Thomas Schmidt

Patricia Gräf

Keenan Bashour

Magdalena Nauerth

The invention provides a method of producing a non-immunogenic (bio)engineered tissue from pluripotent stem cells or pluripotent stem cell derivatives, the respective cells being deficient of MHC class I molecules and comprising an immunomodulatory protein on their surface, wherein the method comprises inducing the differentiation of the pluripotent stem cells into a cell type that is essential for the function of the engineered tissue under conditions that also allow the formation of the engineered tissue, thereby rendering the engineered tissue to be non-immunogenic to a recipient of the engineered tissue. The present invention further relates to an engineered tissue, a pharmaceutical composition comprising the engineered tissue, medical treatments using the engineered tissue and uses of the engineered tissue.

Non-immunogenic engineered tissue and methods of producing and using the same

Provided herein are methods for culturing cells, including stimulating or expanding (proliferating), a plurality of cells in a composition of cells such as a population of lymphocytes. In some aspects, provided methods and reagents for the culturing, such as stimulation or expansion (proliferation), of cell populations involve binding of agents to a molecule on the surface of the cells, thereby providing one or more signals to the cells. In some cases, the reagents are multimerization reagents and the one or more agents are multimerized by reversibly binding to the reagent. In some aspects, the multimerized agent can provide for expansion or proliferation or other stimulation of a population of cells, and then such stimulatory agents can be removed by disruption of the reversible bond. Also provided are compositions, apparatus and methods of use thereof.

Methods for culturing cells and kits and apparatus for same

Provided herein are cell surface conjugates containing a cell surface molecule and at least one agent, such as at least one affinity tag, and engineered cells expressing such cell surface conjugates. In some embodiments, the cell surface molecule does not contain an intracellular signaling domain or is not capable of mediating intracellular signaling. In some embodiments, the cells engineered to contain the cell surface conjugate, such as T cells, further contain a genetically engineered recombinant receptor that specifically binds to antigens, such as a chimeric antigen receptor (CAR). Also provided are methods of detecting, identifying, selecting or targeting cells expressing the cell surface conjugates, such as in connection with methods of manufacturing engineered cells or in connection with administration of such cells to subjects, including methods of adoptive cell therapy.

Cell surface conjugates and related cell compositions and methods

Provided herein are methods that relate, in some aspects, to the incubation or culturing, such as to induce stimulation of expansion (proliferation), activation, costimulation and/or survival, of a composition of cells, such as a population of lymphocytes. In some aspects, provided are methods and reagents for the stimulation, e.g., of expansion (proliferation), survival or persistence, activation, costimulation, or other effect, of cell populations that involve binding of agents to a molecule on the surface of the cells, thereby providing one or more signals to the cells. In some cases, the reagents are reagents containing a plurality of binding sites for agents, such as multimerization reagents, and thus the one or more agents are multimerized by reversibly binding to the reagent, e.g., thereby creating a stimulatory reagent (multimerized agent), having stimulatory agents multimerized thereon. In some aspects, the multimerized agent can provide for expansion or proliferation or other stimulation of a population of cells, and then such stimulatory agents can be removed by disruption of the reversible bond. Also provided are compositions, apparatus and methods of use thereof.

The invention relates to a method of determining the dissociation rate constant (k) of a receptor molecule R on a target cell using a combination of reversible and irreversible cell labeling. The invention further relates to a cell comprising such a receptor molecule R, wherein the cell has bound to it such a combination of cell labeling. The invention further relates to a kit and an apparatus useful in performing the methods of the invention. The invention further relates to a method of isolation a high-avidity T cell.

Combination of reversible and irreversible cell labeling for analizing receptor-ligand krate

The present invention relates to in vitro-methods of expanding a population of cells such as lymphocytes, comprising contacting a sample comprising a population of cells with a multimerization reagent. The multimerization reagent has reversibly immobilized thereon (bound thereto) a first agent that provides a primary activation signal to the cells and optionally, a second agent that provides a co-stimulatory signal. The invention also provides multimerization reagents, kits, arrangements and an apparatus for expanding cells.

Methods, kits and apparatus for expanding a population of cells

The present invention relates to methods of treating a subject with a population of target cells defined by the presence of a specific receptor molecule on the surface; wherein the population of target cells is isolated by a method of reversibly staining the target cells with a detectable label.

Method of reversibly staining a target cell

The present invention relates to methods of reversibly staining a target cell. The invention also relates to methods of isolating a target cell or a target cell population that is defined by the presence of at least one common specific receptor molecule. The invention also provides kits that can be used to carry out the methods of the invention.

Growing community of inventors

Goettingen, Germany

Lothar Germeroth