The present invention relates to compounds (reactive conjugates) for the chemical modification of therapeutic antibodies or proteins. The compounds enable the regioselective attachment of a payload to an antibody or antibody fragment in one single step, thereby producing a modified antibody or modified antibody fragment, which can be used for diagnosing, monitoring, imaging or treating disease.

Pharmaceutical compositions and methods are presented for creating a ternary structure involving a fluorescent molecule, an intermediate carrier molecule, and a larger protein or polymer with a binding site receptive to the intermediate molecule or fluorescent/intermediate complex. The resulting ternary system improves the binding stability of the fluorescent dye to the protein, both in-vivo and in-vitro. This improved stability results in a longer half-life in medical use, enabling improved qualitative and quantitative use of the dye.

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Compositions and formulations comprising peptide conjugate compounds are provided, including native and modified variants of chlorotoxin peptide conjugated to detectable agents or active agents. Methods of detecting and treating vascular lesions, vascular malformations, and vascular abnormalities including cerebral cavernous malformation (CCM) with peptide conjugate compounds are also provided, including methods of imaging and resecting vascular lesions tissues and cells.

Provided here are therapeutically effective pharmaceutical compositions containing one or more TREX2 inhibitors, and more specifically methods of administering TREX2 inhibitors to increase the effectiveness of a chemotherapeutic agent. Also provided here are methods of identifying agents that inhibit the exonuclease activity of TREX2.

Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.

A PSMA-specific agent comprising a compound according to Formula I or Formula II: wherein S.sub.1 is absent or is an organic spacer group comprising 3-10 carbons; A is an amino acid chain comprising 1 to 5 amino acids wherein at least one of the amino acids is selected from glutamic acid and aspartic acid; S2 is absent or is an organic spacer group comprising 1 to 15 carbons and/or 0 to 2 amino acids; I.sub.1 is an imaging group; and I.sub.2 is absent or is an imaging group. The PSMA-specific agents can be used to image PSMA within a tissue region and/or for the treatment of a cancer, such as prostate cancer.

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Cancer treatment methods using thermotherapy and/or enhanced immunotherapy are disclosed herein. In one embodiment, the method comprising the steps of: (i) applying controlled thermal energy at 40-43° C. for a first predetermined time period to damage and weaken tumor cells of a tumor in a patient; (ii) administering pulsed high intensity focused ultrasound (pHIFU) in a first ultrasound mode to the tumor cells in the patient so as to damage the tumor cells without increasing the thermal energy; and (iii) administering low intensity focused ultrasound (LIFU) in a second ultrasound mode to further damage the tumor cells at a temperature of 39-43° C. for a second predetermined time period while performing observation of the tumor cells by ultrasonic thermometry.

Fibroblast activation protein (FAP)-targeting compounds (e.g., conjugates); a method for imaging cancer or fibrosis; and methods for treating an inflammatory disease/disorder and cancer.

Nanoparticles, methods, and kits are provided for supplying nutrients and other therapeutic agents to transplanted cells. Nutrient deprivation is a significant factor which contributes to poor outcome of many cell transplants because cells receive insufficient nutrients until they are able to establish a functional microcirculation to support their metabolic and physiological needs after transplantation. Nanoparticles are provided for use in supplying nutrients and other therapeutic agents to transplanted cells to improve cell survival. Such nanoparticles can be used to supply nutrients and other factors to transplanted cells until the transplanted cells are able to develop a new microcirculation.

The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in methods of treating disease and for imaging of disease.