Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

Disclosed herein is a multiple drugs delivery system and its uses in treating diseases. The multiple drugs delivery system includes, an anti-PEG antibody for directing the PEGylated therapeutic to the treatment site; and a hydrogel for retaining the anti-PEG antibody and/or the PEGylated therapeutic at the treatment site for at least 3 days. The hydrogel is selected from the group consisting of hyaluronan (HA) or a derivative of HA, collagen, gelatin, fibronectin, fibrinogen, alginate, chitosan, and a synthetic biocompatible polymer. The anti-PEG antibody and the hydrogel are present in the mixture in a ratio from about 1:1 (v/v) to 1:100 (v/v). At least two dosages of the PEGylated therapeutic, which may be the same or different, are administered to the subject, with each dosage being given at about 1 hour to about 1 week apart. Accordingly, a novel method of treating a subject having cancer or ischemia disease is also provided.

Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to a target molecule; and (b) an activator domain that detectably modulates tissue regeneration.

Conjugates comprise a drug or probe, a cell binding agent, and a quinone-containing linker. The quinone-containing linker may be reduced intracellularly to trigger release of the drug or probe. These conjugates may selectively deliver a drug or probe to a site of action of interest for local release of the active drug or probe.

Disclosed herein is a multiple drugs delivery system and its uses in treating diseases. The multiple drugs delivery system includes, an anti-PEG antibody for directing the PEGylated therapeutic to the treatment site; and a hydrogel for retaining the anti-PEG antibody and/or the PEGylated therapeutic at the treatment site for at least 3 days. The hydrogel is selected from the group consisting of hyaluronan (HA) or a derivative of HA, collagen, gelatin, fibronectin, fibrinogen, alginate, chitosan, and a synthetic biocompatible polymer. The anti-PEG antibody and the hydrogel are present in the mixture in a ratio from about 1:1 (v/v) to 1:100 (v/v). At least two dosages of the PEGylated therapeutic, which may be the same or different, are administered to the subject, with each dosage being given at about 1 hour to about 1 week apart. Accordingly, a novel method of treating a subject having cancer or ischemic disease is also provided.

Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to a target molecule; and (b) an activator domain that detectably modulates tissue regeneration.

This invention relates to methods and compositions comprising antibodies or fragments thereof comprising a targeting ligand and engineered cytotoxic cells comprising a targeting agent specific for the targeting ligand, for use in inducing cytotoxicity in a cancer cell, in delivering a cytotoxic cell to a cancer cell in a subject, and in treating cancer.

The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) through a linker and optionally, a connector molecule.

The present invention relates to a method of producing a polyomavirus or polyomavirus-derived virus-like particle (VLP) carrying on its surface at least one targeting molecule that binds to a cell of interest, the method comprising the step of contacting the polyomavirus or polyomavirus-derived VLP with (i) the targeting molecule, wherein the at least one targeting molecule is glycosylated with at least one glycosyl residue that is recognised by the polyomavirus or polyomavirus-derived VLP; or (ii) a first interaction molecule, wherein the first interaction molecule is glycosylated with at least one glycosyl residue that is recognised by the polyomavirus or polyomavirus-derived VLP; and the at least one targeting molecule, wherein the at least one targeting molecule is conjugated to a second interaction molecule capable of interacting with the first interaction molecule. The present invention further relates to a polyomavirus or polyomavirus-derived virus-like particle (VLP), wherein the virus or VLP carries on its surface at least one targeting molecule that binds to a cell of interest, as well as to a polyomavirus or polyomavirus-derived VLP obtained or obtainable by the method of the invention. Furthermore, the present invention relates to a composition comprising said polyomavirus or polyomavirus-derived VLP and to the use of the polyomavirus or polyomavirus-derived VLP of the invention or the composition of the invention for use as a medicament. The present invention further relates to a kit comprising the polyomavirus or polyomavirus-derived VLP or the composition of the invention.