Sloan-kettering Institute for Cancer Research

Memorial Sloan Kettering Cancer Center

Cornell University

Massachusetts Institute of Technology

Other

The United States of America As Represented by the Secretary of

University of Missouri

Steven M Larson

Jason S Lewis

Ulrich B Wiesner

Michelle S Bradbury

Andrew A Burns

Oula Penate Medina

Nai-Kong V Cheung

Sarah M Cheal

Gabriela Chiosis

Karl Dane Wittrup

Peter Smith-Jones

Huazhong He

Laura Llauger-Bufi

Joungnam Kim

Naga Vara Kishore Pillarsetty

Hooisweng Ow

Michel Sadelain

Ouathek Ouerfelli

Richard N Kolesnick

Hong Xu

Alice Tzeng

Tony Taldone

Michael R McDevitt

Mahiuddin Ahmed

Thomas P Quinn

NagaVarakishore Pillarsetty

Guangbin Yang

David Ulmert

Jan Grimm

Hong-fen Guo

Joseph Reginald Osborne

Mary L Alpaugh

Erica M Gomes-Dagama

Zhihao Wu

Edward Komin Fung

Sarah M Taldone

Linlin Wang

Keith S Pentlow

Ronald D Neumann

Martin C Graham

Ronald Finn

James C Reynolds

Jorge A Carrasquillo

Sang-gyu Lee

Ken Rivlin

Hoosweng Ow

Pat B Zanzonico

Nagavarakishore Pillarsetty

Andrew Burns

Tom Quinn

Tuula Penate-Medina

Oula Penate-Medina

Daniel L J Thorek

Michael Mcdevitt

Medina Oula Penate

The present disclosure relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to and neutralize the activity of polysialic acid. The antibodies of the present technology are useful in methods for detecting and treating a polysialic acid-associated cancer in a subject in need thereof.

Anti-polysialic acid antibodies and uses thereof

The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MRI), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.

Multimodal silica-based nanoparticles

Described herein are multi-specific binding agents that bind A33 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Also provided herein are methods of using multi-specific binding agents or compositions thereof for the detection, prevention, and/or therapeutic treatment of diseases characterized by expression of the A33 glycoprotein antigen, in particular, colorectal cancer.

Multi-specific antibodies with affinity for human A33 antigen and DOTA metal complex and uses thereof

Described herein are liposome-based nanocarriers that selectively target bone marrow, minimize tumor delivery, and maintain high drug concentrations in bone marrow when compared to conventional systemic delivery. The composition of the liposome-based nanocarriers may also be tuned to selectively target lymph nodes and other reticuloendothelial system organs (e.g., spleen, e.g., liver). Also described herein are methods of imaging and mapping the bone marrow and/or other reticuloendothelial system organs using the described liposome-based nanocarriers. These methods provide high resolution non-invasive and quantitative imaging via PET, which offers advantages over conventional imaging/tracking methods. Furthermore, in certain embodiments, the liposome-based carriers are used to stabilize and deliver radioprotectant/free radical scavenger drugs to the bone marrow, thereby protecting the bone marrow from subsequent radiation exposure, thereby limiting the adverse impact of radiation exposure on the individual.

Bone marrow-, reticuloendothelial system-, and/or lymph node-targeted radiolabeled liposomes and methods of their diagnostic and therapeutic use

This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor.

Uses of labeled HSP90 inhibitors

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 disclosure describes a non-linear compartmental model using PET-derived data to predict, on a patient-specific basis, the optimal therapeutic dose of cargo carrying antibody (e.g., huA33) such as radiolabeled antibody, the antigen occupancy, residency times in normal and malignant tissues, and the cancer-to-normal tissue (e.g., colorectal cancer-to-normal colon tissue) therapeutic index. In addition, the non-linear compartmental model can be readily applied to the development of strategies such as multi-step targeting (MST) designed to further improve the therapeutic indices of RIT.

Systems and methods for determining optimum patient-specific antibody dose for tumor targeting

Purine scaffold Hsp90 inhibitors are useful in therapeutic applications and as radioimaging ligands.

Small-molecule HSP90 inhibitors

Fluorescent silica-based nanoparticles

Hsp90 inhibitors havin are provided havin the formula: (I) with a 2',4&#x2032;,5&#x2032;-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4&#x2032; and 5&#x2032; positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SOalkyl, COO-alkyl, KH, OH, CN, SOX, NO, NO, C&#x2550;SRNSOX, C&#x2550;OR, where Xis F, NH2, alkyl or H, and Ris alkyl, NH, NH-alkyl or O-alkyl, Cto Calkyl or alkoxy; or wherein Xhas the formula &#x2014;O&#x2014;(CH)&#x2014;O&#x2014;, wherein n is an integer from 0 to 2, preferably 1 or 2, and one of the oxygens is bonded at the 5&#x2032;-position and the other at the 4&#x2032;-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands. 

Growing community of inventors

New York, NY, United States of America

Steven M Larson