Thomas Jefferson University

University of Pennsylvania

Tr Associates, L.l.c.

Other

Kahr Medical Ltd.

Mark L Tykocinski

Marjaneh Razmara

Guoxing Zheng

Michal Dranitzki Elhalel

Yosi Gozlan

Noam Shani

Edwin Bremer

Ido Kaminsky

Matthew Charles Weber

Jui-Han Huang

Gregory J Riely

Aoshuang Chen

Provided is a fusion protein comprising a polypeptide component that blocks binding of CD47 to SIRP alpha and a polypeptide that binds to and triggers a TRAIL receptor or Fas. Also provided is a method of treating cancer in a patient comprising administering the fusion protein of the invention to a patient in need of such treatment.

Fusion proteins that facilitate cancer cell destruction

PD1-41BBL fusion proteins are provided. Accordingly, there is provided a PD1-41BBL fusion protein comprising a single amino acid linker between the PD1 and the 41BBL. Also there is provided a PD1-41BBL fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-41BBL fusion protein, host-cells expressing the PD1-41BBL fusion protein and methods of use thereof.

PD1-41BBL fusion protein and methods of use thereof

Provided is a fusion protein comprising an agonist for CD40 and an agonist for OX40. Compositions comprising the fusion protein and methods of use are also provided.

Agonist fusion protein for CD40 and OX40 and methods of stimulating the immune system

Provided are fusion proteins comprising a first domain and a second domain, wherein the first domain comprises a polypeptide that binds to and triggers PD-1 and the second domain comprises a polypeptide that binds to and triggers a TRAIL receptor or Fas. In some embodiments, the polypeptide that binds to and triggers PD-1 comprises at least a portion of the extracellular domain of PD-L1 or PD-L2 and the second domain comprises at least a portion of the extracellular domain of TRAIL or Fas ligand. Also provided are methods for treating autoimmune, alloimmune or inflammatory diseases, and methods for treating cancer, using the fusion proteins.

PD-L1 and PD-L2-based fusion proteins and uses thereof

The present invention provides fusion proteins that act on the glucocorticoid-induced TNFR family-related gene (GITR) and OX40 signaling pathway. In certain aspects, the proteins of the invention are useful in modulating both regulatory T (Treg) cells and effector T (Teff) cells.

Fusion proteins for modulating regulatory and effector T cells

Fusion proteins which act on the OX40/TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, and alloimmune diseases, as well as cancer.

OX40/TRAIL fusion proteins

Fusion proteins which act on the TWEAK and TRAIL signaling axes are provided. The proteins are useful in the treatment or amelioration of autoimmune diseases, particularly multiple sclerosis, as well as other diseases such as alloimmune diseases and cancer.

Fn14/TRAIL fusion proteins and method of treating cancer

Fn14/TRAIL fusion proteins

Novel chimeric proteins are disclosed. The proteins comprise at least two portions. The first portion binds to a first cell and decreases the cell's ability to send a trans signal to a second cell; the second portion sends its own trans signal to the second cell. Methods for making and using these proteins in the treatment of cancer, viral infections, autoimmune and alloimmune diseases are also disclosed, as are pharmaceutical formulations comprising the novel chimeric proteins and genes. Either the proteins themselves or a genetic sequence encoding the protein can be administered. Other methods are also disclosed in which two molecular components result in decrement of a first trans signal from a first cell and the conferring of a second trans signal to a second cell.

Chimeric proteins and methods for using the same

Methods for transferring one or more proteins to a cell are disclosed. The protein or proteins to be transferred are in the form of a fusion protein, and contain at least one domain encoding for a protein or peptide having trans signaling and/or adhesion function. The fusion protein is transferred to a cell by binding to a lipidated protein, which has been incorporated into the cell membrane. In an additional aspect of the invention, methods of making fusion proteins having cis signaling capabilities, as well as the ability to bind with receptors on the cell's own surface, are provided. Fusion proteins incorporating GPI or a homing element, and a costimulator or inhibitor domain can also be directly transferred to the cell surface. Methods for using cells which have undergone protein transfer according to the present methods are also disclosed. This includes use in a cancer vaccine, use for treatment of cancer or autoimmune disease, and use in determining costimulator threshold levels.

Auto-stimulating cells and methods for making and using the same

Novel fusion proteins comprising PP14 are disclosed. The fusion proteins retain the immunoregulatory function of native PP14, but offer significant advantages. Methods for using the fusion proteins, and sequence encoding the same in the treatment of immune system diseases and disorders are therefore also disclosed, as are methods for recombinant production of the present fusion proteins.

PP14 fusion proteins and methods for making and using the same

Methods for transferring one or more proteins to a cell are disclosed. The protein or proteins to be transferred are in the form of a fusion protein, and contain at least one domain encoding for a protein or peptide having trans signaling and/or adhesion function. The fusion protein is transferred to a cell by binding to a lipidated protein, which has been incorporated into the cell membrane. Methods for using cells which have undergone protein transfer according to the present methods are also disclosed. This includes use in a cancer vaccine, use for treatment of cancer or autoimmune disease, and use in determining costimulator threshold levels.

Growing community of inventors

Merion Station, PA, United States of America

Mark L Tykocinski