Abstract: 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.

Abstract: The present invention is directed to ligand like a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for one or more antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8; cell populations expressing such CARs and the use of the cell populations for cancer therapy.

Abstract: The present invention provides FGF-2 polypeptides that differ from the wild-type FGF-2 (SEQ ID NO:1) at least at amino acid position 56, 102 and 119, wherein the differences are Q56I, N102G, K119N substitutions, leading to FGF-2 polypeptides with higher thermostability, higher biological activity and higher resistance to proteolytic degradation. These polypeptides can be used in cell culture media.

Abstract: The invention is directed to a method for detecting a target moiety in a sample of biological specimens by: a) providing at least one conjugate with the general formula (I) Xn—P—Ym, b) contacting the sample of biological specimens with at least one conjugate, thereby labeling the target moiety recognized by the antigen recognizing moiety Y with the conjugate c) exciting the labelled target moieties with light having a wavelength within the absorbance spectrum of fluorescent moiety X d) detecting the labelled target moieties by detecting the fluorescence radiation and e) degrading the fluorescent moiety X of the labelled target moieties by irradiating the conjugate with light having a wavelength within the absorbance spectrum of fluorescent moiety X Use of the method in fluorescence microscopy, flow cytometer, spectrofluorometry, cell separation, pathology or histology

Abstract: The invention is directed to a Perfusion device for biological tissues comprising a casing having two parts, a first part (1) and a second part (9), a holder (7) for a plurality of hollow penetration structures (8), wherein the hollow penetration structures (8) are provided with at least one orifice having fluid communication through the holder (7) a support (5) for the biological tissue (6) characterized in that the support (5) for the biological tissue (6) is positioned in the casing at a distance to the holder (7) that by joining the first part (1) and the second part (9) to form the casing, the hollow penetration structures (8) are in proximity to the holder (7). Use of the perfusion device in a process for disaggregation of a biological tissue to yield target cells.

Abstract: A multilevel, disposable cartridge may have a plurality of fluid wells or reservoirs holding a plurality of reagents, and a sample viewing area to view a biological sample. The reagents may be applied sequentially to the sample by opening a specific valve formed in an elastomeric, flexible layer under the fluid well. The fluid channels may be formed in a first rigid plastic layer to conduct the reagent to the sample. Pneumatic channels for applying suction or pressure to the valves may be formed in a second rigid, plastic layer.

Abstract: The invention relates to a cell modification device, comprising a centrifugation chamber with at least one cell modifying surface with a normal vector having an angle of 135?45° to the rotational axis of the centrifugation chamber, wherein the centrifugation chamber comprises at least one input/output port and the cells to be modified are immobilized at the cell modifying surfaces by the rotation of the centrifugation chamber at 2 to 2000 g.

Abstract: The present invention provides chimeric antigen receptors (CARs) comprising an antigen binding domain specific for SSEA4, a population of engineered cells expressing said CARs, and a pharmaceutical composition comprising said genetically modified cells expressing said CARs. The pharmaceutical composition may be for use of the treatment of cancer in a subject suffering from cancer, wherein at least a subpopulation of the cancerous cells of said cancer expresses SSEA4.

Abstract: The invention is directed to an connector comprising a first part and a second part, each provided with a contact surface and at least one non-contact surface facing away from the contact surface, at least one opening in the contact surface having an fluid connection to at least one opening of the non-contact surface, a releasable covering of the opening in the contact surface, and complementary means for mechanically coupling the parts at the contact surfaces to form the connector. The complementary means for mechanically coupling the parts are configured to mechanically interlock with each other.

Abstract: The invention provides a system that comprises pharmaceutical agents for use in immunotherapy for reducing the side-effects of an antigen-recognizing receptor against antigen-expressing non-target cells in an individual. The system includes an antigen-recognizing receptor that specifically recognizes an antigen on target cells and at least on one hematopoietic cell type in the individual. The antigen-recognizing receptor is exemplified by chimeric antigen receptors (CAR) be expressed on the surface of an immune effector cells. The system also includes hematopoietic cells resistant to recognition of the same antigen by the antigen-recognizing receptor.

Abstract: The invention is directed to a method for detecting a target moiety in a sample of biological specimens by: a) providing at least one conjugate with the general formula (I) Xn—P—Ym, with X is an detection moiety, P an enzymatically degradable spacer and Y an antigen recognizing moiety and n, m are integers between 1 and 100 and wherein X and Y are covalently bound to P; b) contacting the sample of biological specimens with at least one conjugate, thereby labeling the target moiety recognized by the antigen recognizing moiety Y; c) detecting the target moiety labeled with the conjugate with the detecting moiety X; and d) enzymatically degrading spacer P, thereby cleaving the detection moiety X from the conjugate. The method is useful to identify target moieties on the biological specimens. The biological specimens detected by the conjugate can be subsequently removed from the sample.

Abstract: The invention is directed to a releasable conjugate comprising a biotinylated ligand having a biotin moiety, a ligand moiety (Ligand1) and a biotin-binding molecule (bbm) bound to the biotin moiety of the biotinylated ligand. The ligand moiety of the biotinylated ligand may be separated by a spacer group consisting of polyethylene glycol. Furthermore, the invention relates to a method for cleaving the releasable conjugate by providing biotin or streptavidin and an auxiliary release agent in a sufficient concentration to displace the biotin-binding molecule (bbm) from the biotin moiety of the biotinylated ligand and a method for separation of target cells from a cell sample utilizing the conjugate.

Abstract: The present invention provides a process for generation of genetically modified T cells, T cell subsets and/or T cell progenitors comprising the steps: a) providing a cell sample comprising T cells, T cell subsets and/or T cell progenitors b) preparation of the cell sample by centrifugation c) magnetic separation of the T cells, T cell subsets and/or T cell progenitors d) activation of the enriched T cells, T cell subsets and/or T cell progenitors using modulatory agents e) genetic modification of the T cells, T cell subsets and/or T cell progenitors f) expansion of the genetically modified T cells, T cell subsets and/or T cell progenitors in a cultivation chamber g) washing of the cultured T cells, T cell subsets and/or T cell progenitors characterized in that all steps are performed in a closed and sterile cell culture system.

Abstract: The invention is directed to a column system for separation of particles comprising a reservoir section with a input opening; a filter section provided with a filter matrix and an output opening and a plunger having a first and a second end, the first end fitting into the reservoir section characterized in that the plunger is provided with at least one channel providing gaseous communication from the first end to the second end. The column system may be used for magnetic cell separation.

Abstract: The invention relates to a system, comprising: a) a sample processing unit, comprising an input port and an output port coupled to a rotating container having at least one sample chamber, the sample processing unit configured provide a first processing step to a sample or to rotate the container so as to apply a centrifugal force to a sample deposited in the chamber and separate at least a first component and a second component of the deposited sample; and b) a sample separation unit coupled to the output port of the sample processing unit, the cell separation unit comprising separation column holder (42), a pump (64) and a plurality of valves (1-11) configured to at least partially control fluid flow through a fluid circuitry and a separation column (40) positioned in the holder, the separation column configured to separate labeled and unlabeled components of sample flowed through the column.

Abstract: The present invention provides a method for generation of a cell composition of mesencephalic dopaminergic progenitor cells from a starting cell composition comprising pluripotent and/or multipotent stem cells, the method comprising the steps of a) differentiating said pluripotent and/or multipotent stem cells into mesencephalic dopaminergic progenitor cells, thereby generating a cell population comprising mesencephalic dopaminergic progenitor cells and other cells, b) dissociating the differentiated cells of step a) into a single cell suspension, and c) enriching said mesencephalic dopaminergic progenitor cells by using an antigen binding molecule specific for the CD47 antigen for positive selection of said mesencephalic dopaminergic progenitor cells in said single cell suspension. Said method may be performed in a closed cell sample processing system and may be performed in an automated manner.

Abstract: The invention is directed to a centrifuge chamber comprising a cylinder having a base plate and a cover plate, a rotational axis with at least one port for input and/or output of liquids, at least one port for input of gases and at least one layer for cell culturing, wherein the layer for cell culturing comprises a gas-permeable membrane on which cells can be cultured and wherein the at least one port for input and/or output of gases is connected to the gas-permeable membrane.

Abstract: A cell strainer for separating particles from a cell suspension, having an upper portion with at least one filter area lying essentially perpendicular to the direction of flow of the suspension and a lower portion adapted to fit into the openings of at least two sample tubes with different sized openings. The lower portion has a first section with shoulders or flanges having the diameter of the opening of a first tube and a second section having an inner and outer wall serving as a receptacle for the neck of a second tube, where the diameter of the first section is larger than the diameter of the second section.

Abstract: The invention is directed to a process for sorting target cells and non-target cells from a sample by a cell sorting valve microfabricated on a surface of a silicon substrate, with microfabricated channels leading from the cell sorting valve, wherein the cell sorting valve separates the target particles from non-target material; a disposable cartridge containing a sample reservoir, a sort reservoir and a waste reservoir; wherein the sample is provided in a buffer comprising nuclease.

Abstract: A process for depleting host cells from a xenograft of human cells on a murine host is disclosed. The process includes fragmenting the xenograft, subjecting the sample to antibodies specific for a murine CD9 epitope coupled to a detection means, depleting the cell suspension from cells bound by the CD9-antibodies using the detection means, and collecting the cells not bound by the CD9-antibodies as target cells.