University of California

Memgen, Inc.

The University of Texas System

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

Mark J Cantwell

Thomas James Kipps

Charles E Prussak

Sanjai Sharma

Patrick Hwu

Willem Overwijk

Amer A Beg

Manisha Singh

Scott Antonia

Willem W Overwijk

The invention concerns APCs, such as DCs, comprising a combination of an exogenous type I interferon and an exogenous CD40-L or one or more heterologous nucleic acid sequences encoding a combination of an exogenous type I IFN and an exogenous CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such APCs to a subject in need thereof. In certain embodiments, a subject is treated with an irradiation therapy before administering the APCs, such as DCs, of the invention. The invention also concerns an oncolytic virus comprising a combination of a type I IFN and CD40-L or one or more nucleic acid sequences encoding a combination of a type I IFN and CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such oncolytic virus to a subject in need thereof.

Oncolytic virus or antigen presenting cell mediated cancer therapy using type I interferon and CD40-ligand

Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of a TLR agonist and a chimeric CD154 polypeptide. Also provided herein are methods of enhanced immune function.

Methods of CD40 and toll like receptor immune activation

Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.

Replication-enhanced oncolytic adenoviruses

Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one immune checkpoint inhibitor and a chimeric CD 154 polypeptide. Also provided herein are methods of enhanced immune function.

Methods of CD40 activation and immune checkpoint blockade

Disclosed are oncolytic viruses comprising chimeric human/mouse CD40 ligands. The chimeric human/mouse CD40 ligand may be MEM40. The oncolytic virus may be replication competent. The oncolytic virus may be an oncolytic herpes simplex virus. Also disclosed are methods comprising administering an oncolytic virus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from cancer.

Armed oncolytic viruses

The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Chimeric CD154 polypeptides

The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1;, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF&#x3b1;, wherein the encoded domain or subdomain replaces a cleavage site of native TNF&#x3b1;, and a second nucleotide sequence encoding a domain or subdomain of native TNF&#x3b1; that binds to a TNF&#x3b1; receptor. The encoded chimeric TNF&#x3b1; is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF&#x3b1; receptor on the surface of a cell. The chimeric TNF&#x3b1; is therefore useful in methods for inducing apoptosis of a cell expressing a TNF&#x3b1; receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1; that is expressed on the surface of the cell.

Chimeric nucleic acids encoding polypeptides comprising TNF alpha, CD70 and FAS ligand domains

Nucleic acids encoding chimeric CD154 polypeptides

This invention relates to genes which encode accessory molecule ligands and their use for immunomodulation, vaccination and treatments of various human diseases, including malignancies and autoimmune diseases. This invention also describes the use of accessory molecule ligands which are made up of various domains and subdomain portions of molecules derived from the tumor necrosis factor family. The chimeric molecules of this invention contain unique properties which lead to the stabilization of their activities and thus greater usefulness in the treatment of diseases. Vectors for expressing genes which encode the accessory molecule ligands of this invention are also disclosed.

Chimeric nucleic acids encoding polypeptides comprising CD70 and Fas ligand domains

The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1; and chimeric TNF&#x3b1; polypeptides. The former have a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF&#x3b1;, wherein the encoded domain or subdomain lacks a cleavage site, and a second nucleotide sequence encoding a domain or subdomain of native TNF&#x3b1; that binds to a TNF&#x3b1; receptor. The encoded chimeric TNF&#x3b1; is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF&#x3b1; receptor on the surface of a cell. The chimeric TNF&#x3b1; is therefore useful in methods for inducing apoptosis of a cell expressing a TNF&#x3b1; receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1; that is expressed on the surface of the cell.

Nucleic acid molecules encoding TNF-&#x3b1; ligand polypeptides having a CD154 domain

Chimeric nucleic acids encoding polypeptides comprising CD154 and TNF-&#x3b1;

This invention relates to genes which encode accessory molecule ligands, such as the CD40 ligand and their use for immunomodulation, vaccination and treatments of various human diseases, including malignancies and autoimmune diseases. This invention also describes the use of accessory molecule ligands which are made up of various domains and subdomain portions of molecules derived from the tumor necrosis factor family. The chimeric molecules of this invention contain unique properties which lead to the stabilization of their activities and thus greater usefulness in the treatment of diseases. Vectors for expressing genes which encode the accessory molecule ligands of this invention are also disclosed.

Growing community of inventors

San Diego, CA, United States of America

Mark J Cantwell