H. Lee Moffitt Cancer Center and Research Institute, Inc.

The University of Arizona

University of South Florida

The University of Texas System

Intezyne Technologies, Incorporated

Other

The Translational Genomics Research Institute

David L Morse

Robert J Gillies

Josef Vagner

Mark L McLaughlin

Narges Tafreshi

Victor J Hruby

Amanda Huynh

Jonathan L Sessler

Kevin N Sill

Christian Preihs

Natalie M Barkey

Michael Doligalski

Gary V Martinez

Mark Ronald McLaughlin

Scott Antonia

Eugene A Mash

Shari Pilon-Thomas

Haiyong Han

Marilyn M Bui

Robert A Gatenby

Steven Alan Enkemann

Thaddeus Wadas

Ariosto Siqueira Silva

Eric J Ginzburg

Hyun Joo Kil

William Bradford Carter

Arig A Ibrahim Hashim

Parastou Foroutan

Suryakiran Navath

The subject matter disclosed herein relates generally to cancer therapy and to anticancer compounds and imaging agents. More specifically, the subject matter disclosed herein relates to agents that target (X) R and their use in the treatment of cancer.

Delta-opioid receptor targeted agent for molecular imaging and immunotherapy of cancer

The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imagable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Melanocortin 1 receptor ligands and methods of use

Cellular targets on cancer cells have been identified that can be used with targeted molecular imaging to detect the cancer cells in vivo. Non-invasive methods for detecting cancer cells, such as metastasized cancer cells, are therefore provided. Also provided are compositions and kits for use in the disclosed methods.

Molecular imaging of cancer cells in vivo

Disclosed are monoacylated Toll-like receptor 2 ligands which can be used in both the development of targeted agents for the imaging and treatment of pancreatic cancer as well as other cancers, and as an adjuvant for cancer immunotherapy. The monoacylated compounds disclosed herein have a higher binding affinity for TLR2 relative to a known potent diacylated agonists, but only &#x2212;&#xbd; the bioactivity. Competition of the monoacylated compound with the diacylated compound for binding TLR2 was confirmed. Hence, the reported monoacylated compounds are inhibitors/antagonists of TLR2 activation.

Toll-like receptor 2 ligands and methods of making and using thereof

The subject matter disclosed herein relates generally to cancer therapy and to anti-cancer compounds and imaging agents. More specifically, the subject matter disclosed herein relates to agents that target MC1R and their use in the treatment of cancer. Methods of screening for MC1R targeted agents are also disclosed.

Radiotherapeutic and companion imaging agents to target MC1R

The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

Disclosed is CT or MR contrast agent which comprises a base or carrier scaffold formed of a polyhydroxol compound having a linker to which a Gd-DOTA is covalently bonded. Also disclosed is a method of screening a patient for colon cancer using a CT or MR contrast, which method comprises administering to a patient undergoing screening a compound as above described.

Method and compositions for orally administered contrast agents for MR imaging

An axial flux motor has a rotor mounted about an axis of rotation. Permanent magnets are mounted on a first axial face of the rotor and a predetermined encoder pattern is provided on the surface of a second axial face of the rotor. A stator is positioned on one side of the rotor adjacent to the first axial face of the rotor. A sensor is mounted on the other side of the rotor adjacent to the second axial face of the rotor. The sensor outputs signals corresponding to the encoder pattern on the surface of the second axial face of the rotor. A motor control system is coupled to receive the signals from the sensor and calculates a speed of rotation of the rotor based on the signals from the sensor. In addition, the motor control system may calculate rotor position information, relative or absolute, based on the encoder pattern.

Axial flux motor with built-in optical encoder

The current invention pertains to a molecular conjugate comprising an antagonist of a cell surface receptor specific to a target cell and an immune effector, such as a T cell modulator, conjugated to the antagonist. The target cell can be a cell responsible for development of a disease in a subject, for example, a cancer cell. In certain embodiments, the immune effector is an immune effector protein or an immune effector fragment thereof. The current invention also pertains to a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutically effective amount of the molecular conjugates of the current invention to the subject. The methods of the current invention can be used to treat cancer, such as breast cancer, ovarian cancer, prostate cancer, lung cancer, pancreatic cancer, or melanoma.

Conjugates for immunotherapy

The subject matter disclosed herein relates generally to cancer therapy and to anticancer compounds and imaging agents. More specifically, the subject matter disclosed herein relates to agents that target DOR and their use in the treatment of cancer.

A method of treating cancer or inhibiting metastasis in a subject by increasing intratumoral extracellular pH is presented. The method includes administering to the subject a therapeutically effective amount of a buffer having a pKa greater than 6.1. In an advantageous embodiment the pKa of the buffer is about 7.0. Examples of buffers for increasing extracellular pH include NaHCO, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA), cholamine chloride, N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), N-Tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES) and 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES). The method can further include the step of pretreating with one or more chemotherapeutic agents.

Method of increasing intratumoral pHe and reducing acid-mediated invasion

Growing community of inventors

Tampa, FL, United States of America

David L Morse