The Wistar Institute

Dartmouth College

Celdara Medical, LLC

Jose R Conejo-Garcia

Alfredo Perales-Puchalt

Hui Hu

Tom-Li Stephen

Steven N Fiering

Michael Allegrezza

John B Weaver

David J Bzik

Barbara A Fox

Diana G Martinez

Jason Baird

Ebo D De Muinck

Adam M Rauwerdink

Uciane K Scarlett

Eduardo Huarte-Sobrino

Juan Cubillos-Ruiz

Yolanda Nesbeth

A nucleic acid sequence is provided that encodes a chimeric protein comprising a ligand that comprises a naturally occurring or modified follicle stimulating hormone sequence, e.g., an FSHβ sequence, or fragment thereof, which ligand binds to human follicle stimulating hormone (FSH) receptor, linked to either (a) a nucleic acid sequence that encodes an extracellular hinge domain, a transmembrane domain, a co-stimulatory signaling region, and a signaling endodomain; or (b) a nucleic acid sequence that encodes a ligand that binds to NKG2D. The vector containing the nucleic acid sequence, the chimeric proteins so encoded, and modified T cells expressing the chimeric protein, as well as method of using these compositions for the treatment of FSHR-expressing cancers or tumor cells are also provided.

Methods and compositions for treating cancer

A nucleic acid sequence is provided that encodes a chimeric protein comprising a ligand that comprises a naturally occurring or modified follicle stimulating hormone sequence, e.g., an FSH&#x3b2; sequence, or fragment thereof, which ligand binds to human follicle stimulating hormone (FSH) receptor, linked to either (a) a nucleic acid sequence that encodes an extracellular hinge domain, a transmembrane domain, a co-stimulatory signaling region, and a signaling endodomain; or (b) a nucleic acid sequence that encodes a ligand that binds to NKG2D. The vector containing the nucleic acid sequence, the chimeric proteins so encoded, and modified T cells expressing the chimeric protein, as well as method of using these compositions for the treatment of FSHR-expressing cancers or tumor cells are also provided.

Compositions, e.g., therapeutic agents, and methods are provided for modulating gene and protein expression of Forkhead Box protein 1 (Foxp1). The therapeutic agents include short nucleic acid molecules that modulate gene and protein expression of Forkhead Box protein 1 (Foxp1) expression, viral vectors containing such molecules, T cells transduced with these viruses for adoptive therapies, and any small molecules that bind to and inactivate Foxp1. These compounds and methods have applications in cancer therapy either alone or in combination with other therapies that stimulate the endogenous immune system in the environment of the cancer, e.g., tumor.

Methods and compositions for enhancing the therapeutic effect of anti-tumor T cells

A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

Method for treatment of metastatic and refractory cancers and tumors with an inducer that overcomes inhibition of T cell proliferation

A nucleic acid sequence is provided that encodes a chimeric protein comprising a ligand that comprises a naturally occurring or modified follicle stimulating hormone sequence, e.g., an FSHp sequence, or fragment thereof, which ligand binds to human follicle stimulating hormone (FSH) receptor, linked to either (a) a nucleic acid sequence that encodes an extracellular hinge domain, a transmembrane domain, a co-stimulatory signaling region, and a signaling endodomain; or (b) a nucleic acid sequence that encodes a ligand that binds to NKG2D. The vector containing the nucleic acid sequence, the chimeric proteins so encoded, and modified T cells expressing the chimeric protein, as well as method of using these compositions for the treatment of FSHR-expressing cancers or tumor cells are also provided.

The present invention provides attenuatedmutants for use as vaccines in the prevention or treatment of cancer.

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Compositions and methods useful for targeted depletion or modulation of dendritic cells are provided. The compositions and methods can be used to promote healing of ischemia-related injury, including ischemia-reperfusion injury. Disclosed are a variety of dendritic cell-targeted toxins, bone morphogenetic protein 7 (BMP7) agonists, and dendritic cell-targeted transforming growth factor beta 1 (TGF-&#x3b2;1) antagonists, all useful in practicing methods of the invention. The inventive compositions and methods can be used in the treatment of various conditions including myocardial infarction, stroke, and critical limb ischemia.

Dendritic cell modulation in post-ischemic wounds

A method for diagnosing certain types of cancers provides a nanoparticle agent to be uptaken by cancer cells for diagnosis and treatment of certain cancers. A compound containing nanoparticles is directed toward a tumor site, and then a predetermined time period passes to allow the nanoparticles to be uptaken by the cancer cells. Imaging is then performed on the nanoparticles by an appropriate imaging device to determine the concentration of nanoparticles uptaken by the cancer cells. Finally, image data provided by the imaging device is analyzed to determine the concentration of nanoparticles and thereby determine whether a tumor is present. The nanoparticle agent can further be employed as a treatment of certain cancers. After the uptake of nanoparticles into the cells, a predetermined field applied to the nanoparticles for a sufficient period of time activates the magnetic cores of the nanoparticles to include hyperthermia-mediated destruction of the cancer cells.

Magnetic particle imaging (MPI) system and method for use of iron-based nanoparticles in imaging and diagnosis

The invention relates to a CD161 ligand known as Proliferation-Induced Lymphocyte-Associated Receptor (PILAR), which is crucial for a robust expansion of human lymphocytes. PILAR is markedly up-regulated on both CD4 and CD8 T cells upon TCR engagement and increases the expression of anti-apoptotic genes and glucose transporters through CD161, which globally results in a dramatic enhancement of T cell proliferation. Agents which stimulate or block this activity are also provided as are methods for manipulating PILAR signaling in the treatment of disease.

Growing community of inventors

Philadelphia, PA, United States of America

Jose R Conejo-Garcia