Memorial Sloan Kettering Cancer Center

Cornell University

Sloan-kettering Institute for Cancer Research

The City University of New York

Adjuvance Technologies, Inc.

Other

University of Missouri

Tri-institutional Therapeutics Discovery Institute

Jason S Lewis

Ulrich B Wiesner

Michelle S Bradbury

Steven M Larson

Andrew A Burns

Oula Penate Medina

Derek Shieh Tan

David Y Gin

Jeffrey R Gardner

Eric K Chea

Alberto Fernandez-Tejada

NagaVarakishore Pillarsetty

Naga Vara Kishore Pillarsetty

Philip O Livingston

Thomas P Quinn

Thomas Reiner

Govind Ragupathi

Lars Nordstroem

J Tyler Martin

Tom Quinn

Nai-Kong V Cheung

Hooisweng Ow

Charles L Sawyers

Gabriela Chiosis

Tony Taldone

Kai Ma

Zahi A Fayad

Hong Xu

Michael J Evans

Barney Yoo

Charles Rudin

John Poirier

David Ulmert

Maria Contel

Feng Chen

Brian Zeglis

Erica M Gomes-Dagama

Mary L Alpaugh

Giuseppe Carlucci

Wolfgang Weber

Ivo Lorenz

Abdul Khan

Natalia Curado

Alberto Fernandez-tejada

Xinlei Chen

David Andrew

Brandon Nemieboka

Maya Suzuki-Nishijima

Sophie Poty

Christian Brand

Melissa Deri

Lynn Francesconi

Shashikanth Ponnala

Hans Lija

Jan-Philip Meyer

Jacob Lee Houghton

Beatriz Salinas Rodriguez

Brandon Carney

Hoosweng Ow

Medina Oula Penate

Andrew Burns

Edward Fisher

Willem JM Mulder

Michael Evans

Michelle Bradbury

Ulrich Wiesner

Naga Vara Pillarsetty

Nagavarakishore Pillarsetty

Carlos Perez-medina

The present disclosure relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to delta-like protein 3 (DLL3). The antibodies of the present technology are useful in methods for detecting and treating a DLL3-associated cancer in a subject in need thereof.

DLL3-targeting antibodies and uses thereof

Truncated triterpene saponin analogues containing a trisaccharide or tetrasaccharide ester are disclosed. Also disclosed are pharmaceutical compositions comprising truncated saponin analogues and synthetic methods of producing the truncated saponin analogues. Another aspect of the present application relates to a method for immunizing a subject, comprising administering to the subject the pharmaceutical composition comprising a minimal saponin analogue and an antigen.

Minimal saponin analogues, synthesis and use 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

The present application relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, and intermediates thereto. The application also provides pharmaceutical compositions comprising compounds of the present invention and methods of using said compounds or compositions in the treatment of and immunization for infectious diseases.

Triterpene saponin analogues

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 relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to and neutralize the activity of L1-CAM protein. The antibodies of the present technology are useful in methods for detecting and treating a L1-CAM-positive cancer in a subject in need thereof.

Anti-L1-CAM antibodies and uses thereof

The present invention provides methods of monitoring and measuring tumor-associated free PSA ('fPSA') with antibody polypeptides as an indication of androgen receptor signaling. In a particular embodiment, the methods may be used to assess the efficacy of anti-androgen and/or general anti-cancer treatments. The present invention also provides various methods and compositions relating to antibodies that are specific for tumor-associated or intratumoral fPSA. For example, the present invention provides compositions, including pharmaceutical compositions, comprising anti-fPSA antibodies, or fragments or characteristic portions thereof. The present invention further provides various therapeutic and/or diagnostic methods of using anti-fPSA antibodies and/or compositions.

Free PSA antibodies as diagnostics, prognostics and therapeutics for prostate cancer

Antibody-drug-conjugates (ADC) are provided having a structure of: wherein L is PRligand. The ADC has n drug moieties bound to the Trastuzumab antibody such that the ADC has a drug-to-antibody ratio (DAR) between 2 and 4 and the drug moieties are bound to the Trastuzumab antibody through cysteine (S) or lystine (Lys) residues. The disclosed ADCs are particularly useful in treating breast cancer.

Antibody-drug conjugates based on gold compounds

Described herein are Tz/TCO-based pretargeting strategies using an Al[F]-NOTA-labeled tetrazine radioligand. This imaging strategy enables delineation of cancer at earlier time points compared to other imaging strategies and further decreases the radiation dose to healthy tissues compared to directly labeled antibodies. Al-basedF imaging of small molecules, such as tetrazine, has not been previously achieved due to the decomposition of tetrazine during radiofluorination. Radiofluorination is advantageous over other radiolabeling methods because, in addition to having a shorter half-life,F is more readily available to produce and therefore integrated into hospital workflows.

Radioligands for pretargeted pet imaging and methods of their therapeutic use

Described herein is a chelator for radiolabels (e.g.,Zr) for targeted PET imaging that is an alternative to DFO. In certain embodiments, the chelator forZr is the ligand, 3,4,3-(LI-1,2-HOPO) ('HOPO'), which exhibits equal or superior stability compared to DFO in chemical and biological assays across a period of several days in vivo. As shown in FIG., the HOPO is an octadentate chelator that stabilizes chelation of radiolabels (e.g.,Zr). A bifunctional ligand comprising p-SCN-Bn-HOPO is shown in FIG.and FIG.. Such a bifunctional ligand can eliminate (e.g.,Zr) loss from the chelate in vivo and reduce uptake in bone and non-target tissue. Therefore, the bifunctional HOPO ligand can facilitate safer and improved PET imaging with radiolabeled antibodies.

Compositions for therapeutics, targeted PET imaging and methods of their use

Fluorescent silica-based nanoparticles

Growing community of inventors

New York, NY, United States of America

Jason S Lewis