Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Provided herein are novel blocking chimeric antigen receptors (“bCARs”) and immune cells (e.g., effector and regulatory immune cells) that express such bCARs. Such blocking CARs prevent undesired activation of the immune cells, particularly undesired activation of the immune cells against normal tissue in therapeutic applications. Thus, such bCARs advantageously allow for selective immune cell activation only upon interaction with specific target cells (e.g., tumor cell).

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A is nucleic acid sequence encoding a first polypeptide which comprises a first signal peptide; B is nucleic acid sequence encoding a second polypeptide which comprises a second signal peptide and X is a nucleic acid sequence which encodes a cleavage site, wherein the first signal peptide or the second signal peptide comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present disclosure provides compositions and methods for enhancing immunity (or immune response). The compositions and methods are particularly useful for potentiating immune response of a lymphoid cell. The compositions and methods are applicable for treating cancer and other diseases.

The disclosure features isolated polynucleotides, such as mRNAs, encoding a polypeptide that disrupts immune cell activity, such as T cell or B cell activity, including mRNAs comprising one or more modified nucleobase. The immune cell disruptor polynucleotides encode a polypeptide that comprises a first domain that mediates association of the polypeptide with an immune cell component and a second domain that mediates inhibition of immune cell activity when the polypeptide is expressed in the immune cell. The disclosure also features methods of using the same, for example, for inhibiting immune responses when administered to a subject, such as to inhibit autoimmune reactions.

A method for the prevention, treatment, or amelioration of a medical disease or condition associated with inflammation caused by glutamate excitotoxicity comprising administering to a patient a peptide that binds to or interferes with the P38 MAPK-COX2-PGE.sub.2 and ERK MAPK-CX3CL1-sCX3CL1 pathways.

Provided herein, inter alia, are PTPRS de-clustering agents and compositions and kits comprising the agents. Provided are methods of modulating extracellular matrix or decreasing fibroblast activity in a subject. Also provided are methods of treating subjects with or at risk of developing extracellular matrix diseases, fibroblast-mediated diseases, or autoimmune diseases.

The present disclosure provides gRNA compositions, CRISPR/Cas systems comprising the same, and methods of their use in the modification of immune effector cells. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

The present invention relates to a peptide having the sequence from N-terminus to C-terminus X.sub.-.sub.2X.sub.-1ZX.sub.1X.sub.2X.sub.3X.sub.4X.sub.5 wherein Z is tyrosine, phosphotyrosine or a non-natural analogue of phosphotyrosine, such as phosphonodifluoromethyl phenylalanine (F.sub.2Pmp) X.sub.-2 is a hydrophobic amino acid, such as Leu, Ile, Val, Phe, Tyr, Trp and Met X.sub.-1 is any amino acid X.sub.1 is a hydrophobic amino acid, such as Ile, Leu, Val, Phe, Tyr, Trp and Met X.sub.3 is a hydrophobic amino acid, such as Leu, Ile, Val, Phe, Tyr, Trp and Met X.sub.5 is a hydrophobic amino acid, such as Trp, Ile, Val, Phe, Tyr, and Met X.sub.2 and X.sub.4 are anionic amino acids, preferably each independently is Asp or Glu. The peptide inhibits protein-protein interactions of the Src homology 2 domain-containing phosphatase 2 (SHP2), for the treatment of cancer and RASopathies and as a biomedical research tool.