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AssigneesIcahn School of Medicine at Mount Sinai, Memorial Sloan Kettering Cancer Center
InventorsPeter Palese, Adolfo Garcia-Sastre, Dmitriy Zamarin, Jedd D. Wolchok
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Described herein are chimeric Newcastle disease viruses engineered to express an agonist of a co-stimulatory signal of an immune cell and compositions comprising such viruses. Also described herein are chimeric Newcastle disease viruses engineered to express an antagonist of an inhibitory signal of an immune cell and compositions comprising such viruses. The chimeric Newcastle disease viruses and compositions are useful in the treatment of cancer. In addition, described herein are methods for treating cancer comprising administering Newcastle disease viruses in combination with an agonist of a co-stimulatory signal of an immune and/or an antagonist of an inhibitory signal of an immune cell.
A method for treating cancer, comprising administering to a human subject in need thereof a chimeric New Castle Disease Virus (NDV) and an antagonist of an inhibitory receptor of an immune cell, wherein the chimeric NDV comprises a packaged genome comprising a nucleotide sequence encoding a cytokine, wherein the cytokine is expressed by the NDV, wherein the cytokine is IL-12, wherein the inhibitory receptor is PD1, and wherein the antagonist is an antibody that specifically binds to the inhibitory receptor.
A method for treating cancer, comprising administering to a human subject in need thereof a composition comprising a chimeric NDV and a composition comprising an antagonist of an inhibitory receptor of an immune cell, wherein the chimeric NDV comprises a packaged genome comprising a nucleotide sequence encoding a cytokine, wherein the cytokine is expressed by the NDV, wherein the cytokine is IL-12, wherein the inhibitory receptor is PD1, and wherein the antagonist is a monoclonal antibody that specifically binds to the inhibitory receptor and blocks binding to its native ligands.
A method for treating cancer, comprising administering to a human subject in need thereof a composition comprising a chimeric NDV and a composition comprising an antagonist of an inhibitory receptor of an immune cell, wherein the chimeric NDV is of the LaSota strain and the chimeric NDV comprises a packaged genome comprising a nucleotide sequence encoding a cytokine and a nucleotide sequence encoding a mutated F protein with the amino acid mutation L289A, wherein the nucleotide sequence encoding the cytokine is between the P and M genes of the NDV, wherein the cytokine and mutated F protein are expressed by the NDV, wherein the cytokine is IL-12, wherein the inhibitory receptor is PD1, and wherein the antagonist is a monoclonal antibody that specifically binds to the inhibitory receptor and blocks binding to its native ligands.
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