The present application relates to arenavirus particles containing a genome engineered such that an arenaviral open reading frame (“ORF”) is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. The arenavirus particles described herein are genetically stable and provide high-level transgene expression. In certain embodiments, the arenavirus particles are tri-segmented. In particular, described herein is a nucleotide sequence comprising one or more ORFs comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. Also described herein is an arenavirus particle containing a genome engineered such that an arenaviral ORF is sequestered into two or more functional fragments and these fragments are expressed from two or more viral mRNA transcripts. Also described herein is an arenavirus genomic or antigenomic segment engineered such that the transcription thereof results in one or more mRNA transcripts comprising a nucleotide sequence encoding a functional fragment of arenavirus GP, NP, L or Z. The arenavirus particles described herein may be suitable for vaccines and/or treatment of diseases and/or for the use in immunotherapies.

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

Provided are modified arenaviruses and populations thereof, wherein the modified arenaviruses include i) an introduced PPXY domain; ii) an increased number of PPXY domains; iii) a substituted amino acid in place of S41 in a viral Z protein that is not a substrate for a serine or tyrosine kinase, or a combination of i)-iii). A PPXY domain can include a phosphomimetic replacement of the Y amino acid. Modified Old World and New World arenaviruses are included. Arenavirus production is provided using cell cultures that contain a kinase inhibitor that inhibits a kinase that can phosphorylate the Y amino acid of the PPXY domain, or by cells that have disrupted kinase gene expression, or by cells that have a disrupted ESCRT system. Also provided are pharmaceutical formulations that contain modified arenaviruses, and methods of using such formulations for stimulating an immune response hat is fully or partially protective against arenavirus infection.

The invention relates to a mutant of an arenavirus having improved antitumoral properties. The invention also relates to a method of generating such an arenavirus mutant, related pharmaceutical compositions, medical uses, methods of treatment, and isolated proteins and nucleic acids.

The invention relates to a virus particle comprising a lymphocytic choriomeningitis virus (LCMV) S segment and an LCMV L segment, wherein the S segment comprises an open reading frame encoding a glycoprotein derived from LCMV strain WE, and wherein the L segment comprises an open reading frame encoding an L protein derived from LCMV strain Clone13. The invention also relates to related host cells, methods of producing such virus particles, pharmaceutical compositions comprising such virus particles, and medical uses of such virus particles.

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses.Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.

Provided are modified arenaviruses and populations thereof, wherein the modified arenaviruses include i) an introduced PPXY domain; ii) an increased number of PPXY domains; iii) a substituted amino acid in place of S41 in a viral Z protein that is not a substrate for a serine or tyrosine kinase, or a combination of i)-iii). A PPXY domain can include a phosphomimetic replacement of the Y amino acid. Modified Old World and New World arenaviruses are included. Arenavirus production is provided using cell cultures that contain a kinase inhibitor that inhibits a kinase that can phosphorylate the Y amino acid of the PPXY domain, or by cells that have disrupted kinase gene expression, or by cells that have a disrupted ESCRT system. Also provided are pharmaceutical formulations that contain modified arenaviruses, and methods of using such formulations for stimulating an immune response hat is fully or partially protective against arenavirus infection. Also provided is a method for producing a population of arenaviruses that involves culturing cells that i) are infected with a wild type arenavirus, or ii) comprise one or more expression vectors encoding the arenavirus, wherein the cells are characterized by at least one of: a) comprising kinase inhibitor; or b) a modification such that expression of a kinase capable of phosphorylating a tyrosine in a PPXY domain of the arenavirus is inhibited or eliminated, or c) a disrupted ESCRT pathway.

Provided herein are genetically modified arenaviruses suitable as vaccines against neoplastic diseases or cancer. The invention also relates to pharmaceutical compositions and methods for the prevention or treatment of certain infections causing neoplastic diseases or cancer, such as infections with oncogenic viruses. Specifically, provided herein are pharmaceutical compositions, vaccines, and methods of preventing or treating diseases and conditions caused by and associated with infections with Human Papillomavirus (HPV), such as cervical cancer, anogenital cancer, head and neck cancer and skin cancers. Also provided herein are immunotherapies for the treatment of a neoplastic disease, such as a neoplastic disease caused by infection with oncogenic viruses.