Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and an active pharmaceutically active substance and/or label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for prophylaxis, therapy, diagnosis or theragnosis, in particular for prophylactic or therapeutic vaccination, therapy of cancer, particularly metastatic cancer or inflammatory diseases.

Provided are agents comprising a phosphatidylcholine as an active ingredient to serve as a vein-formation promoting agent capable of promoting vein-like morphological change of tumor vessels, a vessel-diameter enlarging agent capable of enlarging the diameter of tumor vessels, a blood vessel-connection promoting agent capable of promoting connection of tumor vessels to each other without mediation of a lysophospholipid receptor, a leukocyte-infiltration promoting agent capable of promoting infiltration of leukocytes throughout a tumor region without mediation of a lysophospholipid receptor, and an antitumor immunostimulatory agent capable of promoting infiltration of leukocytes throughout a tumor region without mediation of a lysophospholipid receptor.

Regulatory T cells (Treg) are engineered to express a chimeric antigen receptor (CAR), that specifically binds folate receptor beta; and are administered to an individual for treatment of inflammation at sites characterized by the presence of activated myeloid cells. Also provided are methods for utilized engineered T regulatory cells to enhance hematopoietic cell transplantation.

The present disclosure relates to erythroid cells that have been engineered to include, e.g., at the surface of the cell, one or more exogenous stimulatory polypeptides, wherein the exogenous stimulatory polypeptides presented are sufficient to stimulate an immune killer cell. The engineered enucleated cells of the present disclosure are useful in methods of activating NK cells and/or CD8+T-cells in a subject in need thereof, such as subjects having cancer or an infectious disease, and in particular cancers or infectious diseases characterized by downregulation of MHC Class I presentation.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction or activation of immune cells. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from a modulated immune response.

Modulators of syndecan-2, such as an antibody to syndecan-2 that cross-links syndecan-2 on the cell surface or a syndiecan-2 polypeptide that interferes with syndecan-2 receptor binding, is used to regulate a Th17 mediated disease such as an autoimmune disease, fibrosis or cancer.