This present invention relates to compounds (e.g., TM4SF1 binding proteins, e.g., anti-TM4SF1 antibodies) that specifically bind to a polypeptide at an epitope including an amino acid sequence of SEQ ID NO: 1. In particular, the compounds of the invention are capable of being internalized into a TM4SF1-expressing cell (e.g., a tumor cell or an angiogenic vasculature endothelial cell) following binding to the epitope of including the amino acid sequence of SEQ ID NO: 1. The invention also provides methods of treating a subject having a disorder associated with pathological angiogenesis with the compounds of the invention.

Agents that inhibit CX3CL1 in endothelial cells to reduce or inhibit immunosuppression mechanisms that are co-opted by cancer cells to evade host immune system, and that reduce immunosuppression in context of therapies that target VEGF-dependent signaling, and methods of use thereof.

Detection of under-expression of selected genes in NK cells is used to confirm a hypoxic tumor microenvironment that is ordinarily suppressive with respect to ADCC and cytotoxic cell killing of NK cells. Most notably, while hypoxia is known to upregulate HIF-1 and genes under the control of HIF-1, hypoxia in a tumor microenvironment led to under-expression of selected genes, including HIF-1. Thus, gene expression analysis of certain genes on NK cells can be used to detect conditions in a tumor that would indicate use of haNK cells.

A peptide that binds specifically to neuropilin-1 (NRP1) without binding to neuropilin-2 (NRP2) is provided. A fusion protein, a fusion antibody, small-molecule drug, a nanoparticle, or a liposome, which comprises the peptide, and a pharmaceutical composition for treating or preventing cancer or angiogenesis-related diseases, and a composition for diagnosing cancer or angiogenesis-related diseases are provided. A polynucleotide encoding the peptide that binds specifically to NRP1 and a method for screening the peptide that binds specifically to NRP1 are provided. An antibody heavy-chain constant region Fc-fused peptide binding specifically to NRP1 has the property of binding specifically to NRP1, and thus when it is administered in vivo, it accumulates selectively in tumor tissue, and widens the intercellular space between tumor-associated endothelial cells to promote its extravasation and increases its tumor tissue penetration.

The present disclosure relates generally to ex vivo primary tumor models prepared from fresh tumor tissues which are useful for screening anti-cancer agents. The fresh tumor tissues are prepared and cultured under suitable conditions to grow an outgrowth of endothelial cells Killing of these endothelial cells by a candidate agent indicates the efficacy of the agent in inhibiting tumor angiogenesis.

The present subject matter provides compositions, formulations, and methods for inhibiting, treating, or preventing aberrant angiogenesis in a subject.

The invention relates to compositions and methods for reducing excessive vascular development and treat related disorders. In one aspect, the invention provides methods for treating, reducing or inhibiting vascular development in a subject in need thereof. The methods of the invention comprises administering to the subject an effective amount of a HK2 depleting agent that decreases the level of expression and/or activity of HK2. In some embodiments, the level of expression and/or activity of fibroblast growth factor receptor (FGFR), FGF ligand and/or FGF signaling is/are decreased. The invention also includes methods for diagnosing excessive vascular development and for measuring the efficacy of a treatment for an excessive vascular development in a subject in need thereof. The invention further includes a pharmaceutical composition for treating or reducing angiogenesis or lymphangiogenesis, comprising a HK2 depleting agent and a pharmaceutical acceptable carrier.

The present application is directed to the use of a VEGF-C inhibitor, a VEGFR-2 inhibitor and/or a VEGFR-3 inhibitor as a prophylactic or therapeutic for the treatment of eye disorders such as a maculopathy and pathogenic ocular neovascularisation. The application is also directed to the use of a VEGF-C measurement from a biological sample from a mammalian subject as a predictive marker, a selected marker, a responsive marker or a tracking marker for a disease or condition selected from the group consisting of a maculopathy and pathogenic ocular neovascularization.

A peptide that binds specifically to neuropilin-1 (NRP1) without binding to neuropilin-2 (NRP2) is provided. A fusion protein, a fusion antibody, small-molecule drug, a nanoparticle, or a liposome, which comprises the peptide, and a pharmaceutical composition for treating or preventing cancer or angiogenesis-related diseases, and a composition for diagnosing cancer or angiogenesis-related diseases are provided. A polynucleotide encoding the peptide that binds specifically to NRP1 and a method for screening the peptide that binds specifically to NRP1 are provided. An antibody heavy-chain constant region Fc-fused peptide binding specifically to NRP1 has the property of binding specifically to NRP1, and thus when it is administered in vivo, it accumulates selectively in tumor tissue, and widens the intercellular space between tumor-associated endothelial cells to promote its extravasation and increases its tumor tissue penetration.

An application of a composition in preparation of a drug for diagnosing infantile hemangioma (IH) and/or monitoring progress and prognosis thereof, and a test kit including the composition and instructions. The composition includes at least one of the following four groups of substances: (1) at least one of a total fatty acid or a total saturated fatty acid or a total mono-unsaturated fatty acid or a specific fatty acid; (2) at least one of specific metabolites; (3) at least one of specific proteins; and (4) at least one of specific lipid subclass substances or lipid molecules. The application and the kit can realize early warning/prediction and early diagnosis of the IH, close monitoring of disease progress, objective evaluation of a treatment effect of the drug, and accurate reflection of prognosis.