The Wistar Institute

Virion Therapeutics, LLC

Other

James M. Wilson

Hildegund C. J. Ertl

Hildegund C J Ertl

Xiang Yang Zhou

Luis C S Ferreira

Marcio O Lasaro

Ying Di Zhang

Colin Stephen Magowan

James M Wilson

This disclosure provides replication-incompetent adenoviral vectors useful in vaccine development and gene therapy. The disclosed vectors comprise a selective deletion of E3 and are particularly useful for preparation of vaccines development and for gene therapy using toxic transgene products that result in vector instability that occurs when the entire E3 domain is deleted.

Adenoviral vectors comprising partial deletions of E3

Chimeric protein constructs including a herpesvirus glycoprotein D (gD) and a heterologous polypeptide that interact with herpes virus entry mediator (HVEM) and enhance and enhance an immune response against the heterologous polypeptide and methods for their use are provided.

Constructs for enhancing immune responses

Provided herein are non-naturally occurring variants of the hepatitis B virus (HBV) Core protein, the HBV polymerase N-terminal domain, and the HBV polymerase C-terminal domain, as well as immunogenic fragments thereof. Fusion proteins comprising the HBV variants fused to a herpes simplex virus (HSV) glycoprotein (gD) sequence, as well as methods of using the fusion proteins, are also provided.

Adenoviral vectors encoding hepatitis b viral antigens fused to herpes virus glycoprotein d and methods of using the same

Adenoviral vectors encoding hepatitis B viral antigens fused to herpes virus glycoprotein D and methods of using the same

Methods for treating cancer are disclosed which comprise administering to a subject T cells which have been pretreated ex vivo or in vitro with a fatty acid catabolism promoter to condition the T cell to use fatty acids rather than glucose for energy production. Still other methods comprise co-administering to a subject having a cancer characterized by a solid tumor (a) an immunotherapeutic composition targeting an antigen or ligand on the tumor cell; and (b) a compound or reagent that promotes the use of fatty acid catabolism by tumor antigen-specific T cells in the tumor microenvironment and/or T cells pretreated ex vivo with the fatty acid catabolism promoter to condition the T cell to use fatty acids rather than glucose for energy production for adoptive cell transfer. Both methods may also employ co-administration of a checkpoint inhibitor.

Methods and compositions for treating cancer

The invention includes compositions and methods of generating a chimpanzee-derived adenovirus AdC6 or AdC7 vector vaccine comprising a deletion of E1, a deletion of E3 ORF3, ORF4, ORF5, ORF6, and ORF7 and a sequence encoding HIV protein gp140, gp160 or Gag, methods of treating and/or preventing or immunizing against HIV and methods of inducing an effector T cell, memory T cell and B cell immune response in a mammal administered the composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a mammal as well as a protein expression system.

Compositions and methods of replication deficient adenoviral vectors for vaccine applications

Contructs for enhancing immune responses

A immunogenic composition is provided for use in methods for treating or preventing the development of a cancer, comprising a nucleic acid sequence encoding a cancer antigen and a nucleic acid sequence encoding fibroblast activation protein (FAP). In one embodiment, the composition comprises a vector comprising a first expression cassette comprising a nucleic acid sequence encoding an antigen of a, operatively linked to an expression control sequence that directs the expression of the antigen in a mammalian host cell. The composition further contains a vector comprising a second expression cassette comprising a nucleic acid sequence encoding fibroblast activation protein (FAP) operatively linked to an expression control sequence directing the expression of FAP in a mammalian host cell. In one embodiment, the cancer is one in which tumor progression depends on the fibroblasts expressing fibroblast activation protein (FAP).

Growing community of inventors

Villanova, PA, United States of America

Hildegund C J Ertl