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AssigneeHookipa Biotech GmbH
InventorsHenning LAUTERBACH, Jörg Christoph LAMPERT, Mohamed HABBEDDINE, Josipa RAGUZ, Timo SCHIPPERS, Sarah SCHMIDT, Sarah AHMADI-ERBER, Sandra ROSSKOPF, Klaus ORLINGER, Igor MATUSHANSKY
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The invention relates to genetically modified arenaviruses suitable for the treatment of neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for treatment of neoplastic diseases and/or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus, wherein the arenavirus has been engineered to include a nucleotide sequence encoding one or more antigenic fragment(s) of mutant KRAS alone or to further include a nucleotide sequence encoding one or more antigenic fragment(s) of a mutated cancer driver gene (e.g., a mutant TP53) or a tumor-associated antigen.
An arenavirus particle, wherein
The arenavirus particle of any of the preceding claims, wherein the mutation in KRAS is A18D, A59E, A59G, A59P, A59T, A59S, A59V, A146P, A146S, A146T, A146V, D119N, G12A, G12C, G12D, G12F, G12L, G12R, G12S, G12V, G13A, G13C, G13D, G13E, G13R, G13S, G13V, K117N, Q61E, Q61H, Q61K, Q61L, Q61P, Q61R or a combination thereof.
The arenavirus particle of any of the preceding claims, wherein the mutation in KRAS is G12A, G12C, G12D, G12R, G12S, G12V, G13D, Q61H, Q61R, A146T or a combination thereof.
The arenavirus particle of any of the preceding claims, wherein the fragment of mutant KRAS is 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids long.
The arenavirus particle of any of the preceding claims, wherein the fragment of mutant KRAS is 18 amino acids long.
The arenavirus particle of any of the preceding claims, wherein the region flanking the mutation at the N-terminus of the antigenic fragment is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids long.
The arenavirus particle of any of the preceding claims, wherein the region flanking the mutation at the N-terminus of the antigenic fragment is 8 or 9 amino acids long.
The arenavirus particle of any of the preceding claims, wherein the region flanking the mutation at the C-terminus of the antigenic fragment is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids long.
The arenavirus particle of any of the preceding claims, wherein the region flanking the mutation at the C-terminus of the antigenic fragment is 8 or 9 amino acids long.
The arenavirus particle of any of the preceding claims, wherein the nucleotide sequence encodes two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 antigenic fragments of mutant KRAS, and wherein each antigenic fragment comprises the mutation of one of the mutant KRAS proteins.
The arenavirus particle of any of the preceding claims, wherein the nucleotide sequence encodes five antigenic fragments of a mutant KRAS, and wherein each antigenic fragment comprises the mutation of one of the mutant KRAS proteins.
The arenavirus particle of any of the preceding claims, wherein the nucleotide sequence is engineered to reduce or remove any CpG and TpA islands.
The arenavirus particle of any of the preceding claims, wherein the arenavirus genome comprises:
The arenavirus particle of any of the preceding claims, wherein the arenavirus particle is derived from lymphocytic choriomeningitis virus (LCMV) or Pichinde virus.
A pharmaceutical composition comprising the arenavirus particle of any of the preceding claims.
A method for treating a neoplastic disease in a subject in need thereof, wherein the method comprises administering to the subject an arenavirus particle, wherein
Dependencies are inferred from the claim text.