Polypeptides comprising functional mutants of an isoform of the human vascular endothelial growth factor A (VEGF-A) folded in a non-natural re-arrangement, where the second and fourth cysteine of the mutant's polypeptide chain is only forming intramolecular bridges, while the seventh and eight are only part of intermolecular bonds. The invention further comprises antigenic preparations containing at least one of these polypeptides, and the pharmaceutical compositions comprising such antigenic preparations and vaccine adjuvants. The antigenic preparations according to the invention are used in the manufacturing of a drug, for the treatment of diseases related to the increment of angiogenesis, inflammation, and immunosuppression, as well as for the restoration of the immune system.

Provided is a fusion polypeptide comprising GDF15 (Growth/differentiation factor 15) and an Fc region of immunoglobulin, a pharmaceutical composition comprising the fusion polypeptide, and a method of increasing in vivo duration of GDF15 comprising fusing with an Fc region of immunoglobulin.

Provided is a fusion polypeptide comprising GDF15 (Growth/differentiation factor 15) and an Fc region of immunoglobulin, a pharmaceutical composition comprising the fusion polypeptide, and a method of increasing in vivo duration of GDF15 comprising fusing with an Fc region of immunoglobulin.

The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.

The invention features compositions featuring (a) one or more of connective tissue growth factor (CTGF) and human C-terminal CTGF peptide; and (b) one or more of insulin and IGF-1; and methods of using such compositions to reduce cardiac tissue damage associated with an ischemic event or to enhance engraftment of a cell in a cardiac tissue.

The invention features compositions featuring (a) one or more of connective tissue growth factor (CTGF) and human C-terminal CTGF peptide; and (b) one or more of insulin and IGF-1; and methods of using such compositions to reduce cardiac tissue damage associated with an ischemic event or to enhance engraftment of a cell in a cardiac tissue.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Recombinant AAV (rAAV) vectors comprising a rAVV genome comprising a heterologous nucleic acid encoding a lysosomal protein, e.g., acid alpha-glucosidase (GAA) polypeptide, and optionally a signal peptide and/or optionally a targeting sequence, e.g., IGF2 targeting peptide, operatively linked to a liver-specific promoter (LSP), enabling the GAA polypeptide to be secreted from the liver and targeted to the lysosomes. Particular embodiments relate to a recombinant AAV (rAAV) vector encoding an alpha-glucosidase (GAA) polypeptide, having a liver secretory signal peptide and a IGF2 targeting peptide that binds human cation-independent mannose-6-phosphate receptor (CI-MPR) or to the IGF2 receptor, permitting proper subcellular localization of the GAA polypeptide to lysosomes. Also encompassed are cells, and methods to treat a lysosomal disease, for example, a glycogen storage disease type II (GSD II) disease and/or Pompe Disease with the rAAV vector.

The present invention relates to a short peptide-based therapeutic agent and a medicinal composition including the same for inhibiting activities of cancer cells, which includes at least one short peptide listed as SEQ ID NOs: 1 and 2, either of which is unglycosylated and has no more than 40 amino acid residues, thereby specifically reducing or inhibiting activities of cancer cells such as the cancer cell proliferation, cancer stemness, cell migration, cancer cell invasion, metastasis or drug resistance.