Sloan-kettering Institute for Cancer Research

Other

Memorial Sloan Kettering Cancer Center

Mcdevitt, Michael, R.

Villa, Carlos, H.

Mulvey, J., Justin

Scheinberg, David, A.

Michael R McDevitt

David A Scheinberg

Dangshe Ma

Rena May

Christophe Antczak

Debjit Chattopadhyay

Jon T Njardarson

George Sgouros

Mark Reid Phillips

Carlos H Villa

J Justin Mulvey

Ouathek Ouerfelli

Steven M Larson

Mark Reid Philips

Guangbin Yang

Sarah M Cheal

Jón T Njardarson

Nima Akhavein

Paul Borchardt

Ronald D Finn

Peter M Smith-Jones

William F Maguire

Simone Alidori

The present disclosure relates generally to methods for treating, preventing, and/or ameliorating chronic kidney disease (CKD) and/or renal injury in a subject in need thereof. In particular, the methods disclosed herein comprise administering a therapeutically effective amount of a pharmaceutical composition comprising at least one Nlrp3 siRNA non-covalently conjugated to sidewall ammonium-functionalized carbon nanotubes (fCNTs), wherein the at least one Nlrp3 siRNA reduces the expression of NLR pyrin domain-containing protein 3 (NLRP3) in a subject diagnosed with, or at risk for CKD and/or renal injury.

Inflammasome-targeted RNA interference approach to treating kidney injury and disease

Provided herein is a one-step method for chelating actinium-225 to a construct comprising a chelator linked to a bio-molecule, such as, an antibody or monoclonal antibody, via a bifunctional ligand in, for example, a 3-arm configuration. Also provided are methods for increasing the radiochemical yield of an actinium-225-chelant-biomolecule complex and for producing a high specific activity actinium-225 complex. The chelation is performed at a physiological temperature, about 37&#xb0; C. Also provided are high specific activity actinium-225 complexes, that is, actinium-225 chelated to the chelator-biomolecule construct and pharmaceutical compositions thereof. Further provided are methods of treating a neoplastic disease or disorder with the actinium-225 complexes.

One-step labeling of antibodies to high specific activity with actinium-225

The present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel DOTA-haptens that may be complexed with a radioisotope (e.g.,Ac). Also disclosed herein are methods of the using the DOTA-haptens of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

Dota-hapten compositions for anti-dota/anti-tumor antigen bispecific antibody pretargeted radioimmunotherapy

The present invention provides soluble single wall nanotube (SWNT) constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble SWNT via a DNA or other oligomer platform attached to the SWNT. These soluble SWNT constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble SWNT constructs.

Single wall nanotube constructs and uses thereof

Functionalized single walled or multi-walled carbon nanotubes (f-CNTs) can be delivered into mammals to targeted organs, such as the kidney and the liver. These f-CNTs may be non-covalently linked or covalently linked to therapeutic agents. In particular, the application delivers carbon nanotube-therapeutic agent conjugates to a target organ, thereby preventing or reducing damages to the organ caused by other agents or procedure.

Method and composition for targeted delivery of therapeutic agents

Provided herein is the two component self-assembly single wall nanotube system and the single wall nanotube construct that is the second component. The two component self-assembly single wall nanotube system has a morpholino oligonucleotide with a targeting moiety followed by a single wall nanotube construct with second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct.

Targeted self-assembly of functionalized carbon nanotubes on tumors

Provided herein are methods for delivering a molecule in situ to a cell and for treating a cancer via the in situ delivery. The methods comprise contacting or administering to the cell, as two separate components, a morpholino oligonucleotide comprising a targeting moiety followed by a single wall nanotube construct comprising second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct. Upon self-assembly of a single wall nanotube complex via hybridization of the first morpholino and second complementary morpholino oligonucleotides at the cell, the payload molecule is delivered. Also provided is the two component self-assembly single wall nanotube system and the single wall nanotube construct comprising the second component.

The present invention discloses methods for treating non-malignant cell diseases by administering to an individual a construct comprising actinium-225 or bismuth-213 and an antigen of a non-malignant cell. Also, provided is a method for treating a solid tumor associated with an abnormal proliferation of cells by targeting an antigen of the tumor-associated vasculature with the constructs.

Alpha emitting constructs and uses thereof

The present invention provides soluble single wall nanotube constructs functionalized with a plurality of a targeting moiety and a plurality of one or more payload molecules attached thereto. The targeting moiety and the payload molecules may be attached to the soluble single wall carbon nanotube via a DNA or other oligomer platform attached to the single wall carbon nanotube. These soluble single wall carbon nanotube constructs may comprise a radionuclide or contrast agent and as such are effective as diagnostic and therapeutic agents. Methods provided herein are to diagnosing or locating a cancer, treating a cancer, eliciting an immune response against a cancer or delivering an anticancer drug in situ via an enzymatic nanofactory using the soluble single wall carbon nanotube constructs.

Single wall nanotube constructs and uses therefor

The present invention discloses alpha particle emitting, radioactive constructs capable of killing large tumors (&#x3e;1 mm in diameter), or other cells involved in human or animal diseases such as virus infected cells, autoimmune cells, or other pathological cells, including normal cells, that are targets for destruction, to achieve a therapeutic result. The alpha-emitting constructs have high specific activity.

Alpha-emitting constructs and uses thereof

The present invention discloses alpha particle emitting, radioactive constructs capable of killing large tumors (&#x3e;1 mm in diameter), or other cells involved in human or animal diseases such as virus infected cells, autoimmune cells, or other pathological cells, including normal cells, that are targets for destruction, to achieve a therapeutic result. The alpha emitting constructs have high specific activity.

Targeted alpha particle therapy using actinium-255 conjugates

The present invention provides a generator capable of producing therapeutic Bismuth-213 doses. Also disclosed are methods of preparing Bismuth-213-labeled compounds using such generator and applications of the labeled compounds.

Growing community of inventors

Bronx, NY, United States of America

Michael R McDevitt