Abstract: A series of recombinant DNA constructs and a method is disclosed for use in immunological therapy in general; and in disrupting T cell receptor (TCR), human leukocyte antigens (HLA) class I and NKG2D (Natural-Killer Group 2, member D) ligand expression in particular, with the effect of producing highly compatible autologous universal T cells for further genetically engineering for allogeneic administration. A Universal T (UT) construct is provided and used, comprising a TCR antibody fragment fused to a transmembrane domain (TMD) and ER retention domain of adenovirus early region 3 glycoprotein E3-19k (E3/19K) (TCR-E3/19K RD). The Universal T (UT) construct can hijack ERAD machinery to arrest TCR and HLA molecules in endoplasmic reticulum (ER) and facilitate their translocation into the cytoplasm for ubiquitination and degradation by proteasomes.

Abstract: The present invention concerns providing chimeric natural killer cell receptor (CNK) constructs, genetically engineered T cells expressing such constructs (CNK-T), genetically engineered natural killer cells expressing such constructs (CNK-NK), and the use of CNK-T and CNK-NK to treat a variety of disease states. Specifically, the CNK are designed to target any types of infected, transformed, autoreactive, senescent and stressed cells overexpressing NKG2D ligands. Compared with native T cells and native natural killer cells, the CNK-T and CNK-NK are shown to have improved sensitivity in initiating cytotoxicity against the tumor cells and viral cells in absence or presence of the second genetically modification. Moreover, by incorporating the CNK into the chimeric antigen receptor (CAR) system, the genetically engineered T cells expressing such constructs (CNK/CAR-T) display enhanced sensitivity and superior cytotoxicity against tumor cells.

Abstract: Provided are a universal T cell (CNK-UT) and an application thereof. The CNK-UT has the broad-spectrum ability to recognize and kill tumor cells and virus-infected cells.

Abstract: The invention discloses chimeric endocytic receptor CER-based constructs for activating and regulating immune response, and method for using the same. The CER-based constructs are based on the structure of Fc?RI/? chain and incorporate high-affinity binding domain from receptors or antibodies shown to uptake specific antigen and present the antigen to T cells or B cells to initiate the antigen-specific immune response, Such design has the ability to transform native monocytes or T cells to CER-expressing monocytes (CER-M) or CER-expressing T cells (CER-T) in recognizing and uptake the target antigen and activate subsequent immune responses. Such engineered CER-M or CER-T can be used to treat tumor, viral diseases and autoimmune diseases directly. The endocytosis process with involvement of FcR-? may enhance and coordinate T cell activation in combination with T cell activation by other types of constructs such as CAR.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Abstract: A series of recombinant DNA constructs and a method is disclosed for use in immunological therapy in general; and in disrupting T cell receptor (TCR), human leukocyte antigens (HLA) class I and NKG2D (Natural-Killer Group 2, member D) ligand expression in particular, with the effect of producing highly compatible autologous universal T cells for further genetically engineering for allogeneic administration. A Universal T (UT) construct is provided and used, comprising a TCR antibody fragment fused to a transmembrane domain (TMD) and ER retention domain of adenovirus early region 3 glycoprotein E3-19k (E3/19K) (TCR-E3/19K RD). The Universal T (UT) construct can hijack ERAD machinery to arrest TCR and HLA molecules in endoplasmic reticulum (ER) and facilitate their translocation into the cytoplasm for ubiquitination and degradation by proteasomes.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Abstract: The present disclosure provides tag-specific fusion proteins for selectively detecting molecules containing a strep-tag peptide or cells containing a strep-tag peptide. Disclosed embodiments include tag-specific fusion proteins that can be used in reagents and methods for monitoring and/or modulating immunotherapy cells that express a strep-tag peptide. Embodiments including fusion proteins that specifically bind tagged targets and recombinant host cells comprising polynucleotides encoding the tag-specific fusion proteins are also provided. Immunotherapy cells that express a tagged marker are also provided.

Abstract: The present invention concerns providing chimeric natural killer cell receptor (CNK) constructs, genetically engineered T cells expressing such constructs (CNK-T), genetically engineered natural killer cells expressing such constructs (CNK-NK), and the use of CNK-T and CNK-NK to treat a variety of disease states. Specifically, the CNK are designed to target any types of infected, transformed, autoreactive, senescent and stressed cells overexpressing NKG2D ligands. Compared with native T cells and native natural killer cells, the CNK-T and CNK-NK are shown to have improved sensitivity in initiating cytotoxicity against the tumor cells and viral cells in absence or presence of the second genetically modification. Moreover, by incorporating the CNK into the chimeric antigen receptor (CAR) system, the genetically engineered T cells expressing such constructs (CNK/CAR-T) display enhanced sensitivity and superior cytotoxicity against tumor cells.

Abstract: The invention discloses chimeric endocytic receptor CER-based constructs for activating and regulating immune response, and method for using the same. The CER-based constructs are based on the structure of Fc?RI/? chain and incorporate high-affinity binding domain from receptors or antibodies shown to uptake specific antigen and present the antigen to T cells or B cells to initiate the antigen-specific immune response, Such design has the ability to transform native monocytes or T cells to CER-expressing monocytes (CER-M) or CER-expressing T cells (CER-T) in recognizing and uptake the target antigen and activate subsequent immune responses. Such engineered CER-M or CER-T can be used to treat tumor, viral diseases and autoimmune diseases directly. The endocytosis process with involvement of FcR-? may enhance and coordinate T cell activation in combination with T cell activation by other types of constructs such as CAR.

Abstract: The present disclosure provides immunoglobulin binding proteins and fusion proteins that specifically bind to a strep tag peptide, such as a peptide having the amino acid sequence set forth in SEQ ID NO: 19. Also provided are methods for using the disclosed compositions in a cellular immunotherapy wherein the therapeutic cells express a tag peptide.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Abstract: The present application discloses a final joint of an immersed tunnel, a prefabrication method and an installation method, wherein the final joint includes two end surfaces connected with installed adjacent tube sections; the two end surfaces are both tilted surfaces, so that the longitudinal profile of the final joint along an installation direction is of an inverted trapezoid structure; and the final joint further may be of a structure with a tube section I and a tube section II which are connected with each other.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated using the tag. An exemplary receptor molecule is a chimeric antigen receptor (CAR) having an extracellular domain comprising a binding domain for a target, a hinge region, and a tag cassette, a hydrophobic portion as a transmembrane domain and an intracellular part with an effector domain. An exemplary target is CD19. An exemplary tag is a Strep Tag®. T cells recombinantly modified for expression of such molecules may be used in adoptive immunotherapy.

Abstract: The present application discloses a final joint of an immersed tunnel, a prefabrication method and an installation method, wherein the final joint includes two end surfaces connected with installed adjacent tube sections; the two end surfaces are both tilted surfaces, so that the longitudinal profile of the final joint along an installation direction is of an inverted trapezoid structure; and the final joint further may be of a structure with a tube section I and a tube section II which are connected with each other.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated using the tag. An exemplary receptor molecule is a chimeric antigen receptors (CARs) having an extracellular domain comprising a binding domain for a target, a hinge region and a tag cassette, a hydrophobic portion as a transmembrane domain and, an intracellular part with an effector domain. An exemplary target is CD19, an exemplary tag is a Step-tag. T cells recombinantly modified for expression of such molecules may be used in adoptive immunotherapy.