This invention relates generally to bifunctional molecules including (a) a TGFβRII or fragment thereof capable of binding TGFβ and (b) an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1), uses of such molecules (e.g., for treating cancer), and methods of making such molecules.

The present invention relates to use of a fusion protein in the treatment of age-related macular degeneration. In particular, the present invention relates to use of a bispecific fusion protein inhibiting the activation of a complement pathway and a vascular endothelial growth factor (VEGF) pathway for the treatment of age-related macular degeneration. The present invention also relates to a pharmaceutical composition comprising the fusion protein and a method for treating age-related macular degeneration using the fusion protein.

The invention provides, for the first time, strategies to inhibit the killing of transplanted cells by activated polymorphonuclear cells (PMNs) of the recipient. Multiple different modes for PMN inhibition are provided and one or more agents effectively utilized every mode of action. The combination of two or more of those agents with different modes of action synergistically improved the efficacy of PMN inhibition without exerting toxic side effects on the survival of the target cells. The cells may be pluripotent cells, including hypoimmune pluripotent cells (HIP), ABO blood type O Rhesus Factor negative HIP cells (HIPO−), or derivatives thereof. The cells may also be alpha 1 antitrypsin (A1AT) secreting cells.

The present disclosure provides use of transferrin, a transferrin receptor and an antibody thereof in the preparation of an anti-SARS-CoV-2 drug. Use of the transferrin, the transferrin receptor or the transferrin receptor antibody in the preparation of an anti-SARS-CoV-2 drug is provided. Both surface plasmon resonance (SPR) and immunofluorescence confirm that the SARS-CoV-2 binds to the transferrin receptor through SARS-CoV-2 spike protein; the transferrin and/or the transferrin receptor antibody competitively bind(s) to the transferrin receptor of the body, or the transferrin receptor competitively binds to a site of the SARS-CoV-2 to inhibit binding of the SARS-CoV-2 to the transferrin receptor of the body; thus, the opportunity that the SARS-CoV-2 infects cells is blocked, and the antiviral effect of the body is realized. Use of the transferrin, the transferrin receptor and the antibody thereof in the preparation of a SARS-CoV-2 spike protein-binding biological product is provided

Provided herein, inter alia, are compositions for the modulation of epithelium function, the compositions comprising EphrinA3 protein or EphrinA2 protein, fusions thereof, fragments thereof, or oligonucleotides encoding the same. Also provided are methods for modulating epithelium function, the methods comprising administration of compositions provided herein, including embodiments thereof.

Disclosed are compositions and methods for treating disease or condition caused or exacerbated by S100A9 activity, such as myelodysplastic syndromes (MDS) using a composition comprising an effective amount of a CD33/S100A9 inhibitor.

Disclosed herein is an agent that modulates a cis interaction between Repulsive Guidance Molecule A (RGMa) and Neogenin or lipid rafts. Modulation by the agent may include blocking the cis interaction between RGMa and Neogenin and/or disrupting lipid rafts. In turn, this promotes neuronal cell survival and axon growth and/or regeneration. Also disclosed herein is a method of treating a disease in a subject in need thereof. The method may include administering the agent to the subject. Further disclosed herein is a method of identifying an agent that modulates the cis interaction between RGMa and Neogenin.

The present disclosure provides a method for treating depression using a therapeutically effective amount of a pharmaceutical agent. The pharmaceutical agent can inhibit an activity of an astroglial potassium channel, and especially inhibit the functionality of Kir4.1, in astrocytes in the lateral habenula of a subject so that the abnormal burst firings of neurons in the lateral habenula of the subject can be suppressed. The pharmaceutical agent can include a vector expressing a target nucleotide sequence in the astrocytes in the lateral habenula, whose expression is configured to suppress Kir4.1 expression by RNA interference, or to block Kir4.1 functionality by a dominant negative effect of a mutant Kir4.1 protein. The pharmaceutical agent can alternatively comprise a small molecule compound, or an active macromolecule such as an anti-Kir4.1 antibody, that can directly inhibit the astroglial potassium channel activity.

Compositions and methods for treating malignant gliomas such as glioblastoma are provided, comprising a combination of a peptide conjugate comprising an amino acid sequence derived from the N-terminus of the receptor PAR-1, and the chemotherapeutic agent temozolomide.

Compositions and methods for treating malignant gliomas such as glioblastoma are provided, comprising a combination of a peptide conjugate comprising an amino acid sequence derived from the N-terminus of the receptor PAR-1, and the chemotherapeutic agent temozolomide.