The present invention includes compositions and methods comprising CART cells with SHP-1 and/or SHP-2 genes knocked out.

The present invention provides an artificial synthetic cDNA (complementary deoxyribonucleic acid). The said artificial synthetic cDNA encodes a fused protein which is specifically presented in secondary glioblastoma, and the said artificial synthetic cDNA can be used as a biomarker for detecting the secondary glioblastoma. The present invention further provides a method for detecting secondary glioblastoma. According to the above technical solutions, the accuracy in distinguishing the secondary glioblastoma from primary glioblastoma is effectively improved in the present invention.

The present invention relates to a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the first CAR is an activating CAR comprising an activating endodomain and the second CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain; wherein the first CAR binds to a first antigen and the second CAR binds to a second antigen, wherein both the first and second antigens are expressed on the surface of a target cell; wherein the first CAR binds to an epitope on the first antigen which is relatively proximal to the membrane of the target cell, the second CAR binds to an epitope on the second antigen which is relatively distal to the membrane of the target cell, in comparison with the epitope of the first antigen; and wherein the spacer of the first CAR is an equivalent size to the spacer of the second CAR.

The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

Provided is a method for measuring tyrosine phosphatase and tyrosine kinase activity, as a high-sensitivity measuring method, which is suitable for high throughput and which uses a compound represented by general formula (I) (in the formula, A represents a conjugated ring; L represents a linker or the like having a labeling substance at an end; R.sup.1 represents a hydrogen atom or the like; and R.sup.2 and R.sup.3 each represent a hydrogen atom, an alkyl group or the like).

Provided herein are oligomeric compounds with conjugate groups targeting apolipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a) [apo(a)]. In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Provided herein are recombinant nucleic acids encoding chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX. Also provided are systems of chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX, cells expressing such proteins and shRNA, and methods of use thereof.

The purpose of the present disclosure is to provide a technique that can contribute to less invasive or more reliable diagnosis of lymphocytic anterior hypophysitis and its related diseases. For this purpose, the KCNMA1 (calcium-activated potassium channel subunit alpha-1) protein or an epitope thereof is used as a diagnostic agent for lymphocytic anterior hypophysitis.

The present application provides novel fusion proteins for dephosphorylating proteins that regulate T cell activation through the TCR signaling pathway, nucleic acids encoding said proteins, vectors comprising said nucleic acids, compositions comprising said nucleic acids or vectors, host cells comprising said nucleic acids, vectors or compositions or related pharmaceutical compositions. The present application also provides methods for dephosphorylation of proteins that regulate T cell activation through the TCR signaling pathway of a cell, methods of producing a cell having dephosphorylated proteins that regulate T cell activation through the TCR signaling pathway (e.g. a CAR T cell having dephosphorylated Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) of endogenous CD3), methods of treating a disease, and methods of reducing or preventing GvHD in a subject associated with the administration of one or more CAR T-cells to the subject.