Provided is a method of preventing, treating or delaying progression of a disease involving aberrant fibroblast proliferation. The method involves using a compound that reduces the level of tyrosine phosphatase activity effected by the protein EYA1A in the parenchymal organ, a nucleic acid ligase IV inhibitor, or an antisense oligonucleotide against the p53-binding protein 1 (53BP1).

A tyrosine phosphatase sigma (PTPsigma)-Fc fusion protein comprises a PTPsigma-derived protein and an immunoglobulin (Ig)-derived Fc domain, which can inhibit the signal transduction of PTPsigma by blocking the interaction of the extracellular domain of PTPsigma with a ligand. The PTPsigma-Fc fusion protein inhibits PTPsigma-mediated signaling and as such, can promote the growth of blood stem cells, and can be used for preventing or treating PTPsigma-mediated diseases. Controlling the signal transduction of PTPsigma by utilizing interaction between proteins, the PTPsigma-Fc fusion protein can overcome the problems of conventional inhibitors targeting the active site of PTP. In addition, the solubility of the fusion protein in an aqueous solution can be improved by introducing a mutation thereinto, which makes it possible to apply a high dose to the treatment of the human body and animals.

The present invention generally relates to methods of activating cells via the inhibition of PTP1B and PTPN2 for use in therapy. For example, the invention relates to preparing cells ex vivo for use in immunotherapy, particularly cancer immunotherapy. More specifically, the invention relates to methods for the preparation of leukocytes, particularly T cells, exhibiting cytotoxic properties for use in adoptive cell transfer. The invention also relates to cells and compositions including them for cancer immunotherapy. The invention also relates to methods of immunotherapy, particularly cancer immunotherapy.

The invention relates to compositions and methods of constructs comprising a SIRP-α polypeptide, including SIRP-a variants. The constructs may be engineered in a variety of ways to respond to environmental factors, such as pH, hypoxia, and/or the presence of tumor-associated enzymes or tumor-associated antigens. The constructs of the invention may be used to treat various diseases, such as cancer, preferably solid tumor or hematological cancer.

The present disclosure describes systems and methods for immunotherapies Immune cells can be engineered to exhibit enhanced half-life as compared to control cell (e.g., a non-engineered immune cell). Immune cells can be engineered to exhibit enhanced proliferation as compared to a control cell. Immune cells can be engineered to effectively and specifically target diseased cells (e.g., cancer cells) that a control cell otherwise is insufficient or unable to target. The engineered Immune cells disclosed herein can be engineered ex vivo, in vitro, and in some cases, in vivo. The engineered Immune cells that are prepared ex vivo or in vitro can be administered to a subject in need thereof to treat a disease (e.g., myeloma or solid tumors). The engineered Immune cells can be autologous to the subject. Alternatively, the engineered immune cells can be allogeneic to the subject.

The present invention relates to an expression system for systemic administration comprising a sequence encoding a protein, said expression system allowing: the expression at a therapeutically acceptable level of the protein in the target tissues including skeletal muscles; and the expression at toxically acceptable level of the protein in tissues other than the target tissues, especially in the heart.

The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

Provided herein are chimeric inhibitory receptor constructs and compositions, and cells comprising the same. Also provided are methods of using chimeric inhibitory receptor constructs and compositions, and cells comprising the same.

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.