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: Systems and methods are described for analyzing a plurality of biological samples with a plurality of fluorescent reagents in an automated fashion. The system may include two optical systems, a fluorescence imaging system and an optical quenching system. These two systems may be placed laterally adjacent to one another, and generally beneath one of the wells of sample-containing microtiter plate. The biological sample contained therein may be stained with a series of fluorescent reagents, with the fluorescence quenched between stainings. By precise positioning of the sample with respect to the imaging system, the sample may be imaged with a plurality of serially applied reagents.

Abstract: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

Abstract: 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. In an embodiment, the device is used as a point-of-care and/or portable device. Further, the present disclosure describes software that, when executed by a processor, causes the device to perform the disclosed functions.

Abstract: The present invention provides a combination of compositions comprising i) a composition comprising I) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a stem cell antigen and/or, II) ?) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a tag of a tagged polypeptide, wherein said tagged polypeptide binds specifically to a stem cell antigen, and ?) said tagged polypeptide, and ii) a composition comprising a) a population of CD34+ hematopoietic stem cells, and b) one or more accessory or contributory cell populations selected from the group consisting of myeloid cell lineages expressing CD14, CD11b, CD11c, CD123, CD33; CD36; CD47, CD66b, CD235a, CD146 and CD326. A method applying these compositions to a subject in need thereof are also provided.

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: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

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: 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 present invention provides a composition comprising an isolated polypeptide having non-specific nuclease (NSN) activity for degrading nucleic acids comprising or consisting of at least 70% amino acid sequence identity to SEQ ID NO:2, wherein said polypeptide has NSN activity in a solution of about 4° C., and a cation complexing agent such as EDTA. Said composition may have preferentially a neutral to basic pH. A kit comprising said composition and a method using said composition are also disclosed.

Abstract: The invention is directed to disposable cartridge for electroporation of cells, comprising a fluid compartment in an interior of the disposable cartridge; a first fluid port for providing cell suspension to the fluid compartment, and a second fluid port for delivering a fluid comprising at least one compound to be electroporated into the cells to the fluid compartment; a first electrode and a second electrode disposed in the fluid compartment; at least one exit port which delivers the fluid from the fluid compartment wherein the first and second fluid port have a fluid communication to a mixing channel which has a fluid communication to the fluid compartment, and a third ground electrode and a fourth ground electrode.

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 detection reagent for CAR expressing cells according to general formula (1) Xn—Sm—Do wherein X is a polypeptide comprising at least 20 amino acids of which at least two amino acids are connected by at least one disulfide group S is a spacer comprising at least 15 carbon atoms D is a detection moiety m, o are integers independently between 1 and 200 n is an integer between 4 and 200 with the provisio that X binds to the antigen binding domain of a chimeric antigen receptor of a cell. The detection agent can be used in a method to detect cells having an antigen binding domain of a chimeric antigen receptor (CAR) binding the detection reagent and preferable to remove the detection moiety D from the detected cell.

Abstract: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

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: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

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 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: Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

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.