Abstract: The present invention provides an immune effector cell that comprises a chimeric antigen receptor (CAR) specific for a tag of a tagged polypeptide, wherein said polypeptide binds to an antigen of a target cell, and a chimeric costimulatory receptor (CCR) specific for a further antigen. The CCR is not able to mediate said immune response on its own but boosts the immune response of said immune effector cell triggered by the CAR.

Abstract: The present invention provides an immune effector cell that comprises a chimeric antigen receptor (CAR) specific for a tag of a tagged polypeptide, wherein said polypeptide binds to an antigen of a target cell, and a chimeric costimulatory receptor (CCR) specific for a further antigen. The CCR is not able to mediate said immune response on its own but boosts the immune response of said immune effector cell triggered by the CAR.

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 conjugate complex for detecting a target moiety in a sample of biological specimens having the general formula (I) An - Bm...Cq-Xo (I) with A: antigen recognizing moiety; B: first binding moiety C second binding moiety X: detection moiety; n, m, q, o integers between 1 and 100, wherein B and C are non-covalently bound to each other characterised in that B comprises a thiamine unit and C is a moiety recognizing thiamine. Futher, the invention is directed to a method detecting a target moiety in a sample of biological specimens with a conjugate complex having the general formula (I).

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 process for providing a cell comprising a chimeric antigen receptor (CAR) specific for one or more target antigens exposed on tumor microenvironment cells characterized by providing a cell sample comprising tumor microenvironment cells and non-tumor microenvironment cells and repeating the steps of—contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety—removing unbound conjugate from the cell tissue and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates—erasing the fluorescence emitted by the fluorescent moieties of the conjugates until identifying at least two conjugates provided with antigen recognizing moieties recognizing different antigens, allowing in combination to discriminate between tumor microenvironment cells and non-tumor microenvironment cells and providing cells with the identified at least two antigen recognizing moieties as chimeri

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 present invention provides a method for the generation of genetically modified T cells comprising the steps a) a sample provided comprising T cells, b) preparation of said sample by centrifugation, c) enrichment of the T cells, d) activation of the T cells using modulatory agents, e) genetic modification of the T cells by transduction with lentiviral vector particles, f) removal of said modulatory agents, thereby generating a sample of genetically modified T cells, wherein said method is performed in equal or less than 144 hours, less than 120 hours, less than 96 hours, less than 72 hours, less than 48 hours, or less than 24 hours. In one embodiment of the invention said enrichment of T cells is performed by magnetic cell separation using magnetic particles that are directly or indirectly coupled to antibodies or antigen binding fragments thereof specific for CD4 and/or CD8 wherein said magnetic particles can be removed from the cells after separation.

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: 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 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) An-P-Bm-Cq-Xo??(I) with A: antigen recognizing moiety; P: enzymatically degradable spacer; B: first binding moiety C second binding moiety X: detection moiety; n, m, q, o integers between 1 and 100, wherein B and C are non-covalently bound to each other and A and B are covalently bound to P b) labelling the target moiety recognized by the antigen recognizing moiety A with at least one conjugate c) detecting the labelled target moiety via detecting moiety X d) cleaving Cq-Xo by disrupting the non-covalent bond between Bm and Cq from the labelled target moiety e) cleaving the binding moiety Bm from the labelled target moiety by enzymatically degrading spacer P. The method is useful to identify target moieties on the biological specimens.

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) An-P-Bm-Cq-Xo??(I) ?with A: antigen recognizing moiety; P: enzymatically degradable spacer; B: first binding moiety C second binding moiety X: detection moiety; n, m, q, o integers between 1 and 100, wherein B and C are non-covalently bound to each other and A and B are covalently bound to P b) labelling the target moiety recognized by the antigen recognizing moiety A with at least one conjugate c) detecting the labelled target moiety via detecting moiety X d) cleaving Cq-Xo by disrupting the non-covalent bond between Bm and Cq from the labelled target moiety e) cleaving the binding moiety Bm from the labelled target moiety by enzymatically degrading spacer P. The method is useful to identify target moieties on the biological specimens.

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: The present invention provides an immune effector cell that comprises a chimeric antigen receptor (CAR) specific for a tag of a tagged polypeptide, wherein said polypeptide binds to an antigen of a target cell, and a chimeric costimulatory receptor (CCR) specific for a further antigen. The CCR is not able to mediate said immune response on its own but boosts the immune response of said immune effector cell triggered by the CAR.

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 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 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 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.