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.

This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues.

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.

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. Furthermore, the present invention relates to a composition comprising such a 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.

Disclosed are compositions and methods for treating cancers characterized by the presence of solid tumors, which simultaneously target a plurality of targets on cancer cells using single CAR T construct.

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 damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.

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.

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.

This disclosure provides IR700-molecule conjugates and methods of their use to remove (e.g., separate or isolate) a target from a sample in vivo or from a subject in vitro. It is shown herein that exposure of IR700 to near infrared (NIR) light removes a portion of IR700, changing it from a hydrophilic molecule, to one that is hydrophobic, resulting in aggregation of IR700 and anything bound to it. For example, the disclosed IR700-molecule conjugates and methods provide photo-controlled ways to control the pharmacokinetics of a drug in vivo, and can be used to remove undesired agents from environmental or food samples or to isolate target molecules in a laboratory.