Compositions and methods of use of an oncolytic vesicular stomatitis virus
First Claim
1. An isolated oncolytic VSV virus comprising one or more changes in nucleic acid sequence resulting in substitution of the serine at codon 126 of SEQ ID NO. 3, with an amino acid selected from the group consisting of alanine (A), arginine (R), asparagine (N), aspartic acid (D), cysteine (C), glutamine (Q), glutamic acid (E), glycine (G), histidine (H), isoleucine (I), leucine (L), lysine (K), methionine (M), phenylalanine (F), proline (P), tryptophan (W), or valine (V) and substitution of aspartic acid (D) at codon 223 of SEQ ID NO. 5 with an amino acid selected from the group consisting of serine (S), threonine (T), or tyrosine (Y).
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Abstract
Oncolytic VSV viruses have been developed as a strategy for combating cancer. The present invention includes mutant VSV that have one or more mutations in the nucleic acid sequence encoding the viral genome that increase the oncolytic potential of the virus. Pharmaceutical compositions including oncolytic virus disclosed herein are also provided. Pharmaceutical compositions containing virus and one or more excipients may be for systemic or local administration. Methods of administering an effective amount of the compositions for treating cancer are disclosed. Preferred routes of administration include intratumeral and intravenous injection, and intranasal delivery. Administration of the disclosed compositions containing oncolytic viruses may be coupled with surgical, radiologic, other therapeutic approaches to treatment of cancer. Methods of manufacturing mutant VSV viruses exhibiting desired properties include applying selective pressure, and through directed or random mutagenesis.
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Citations
13 Claims
- 1. An isolated oncolytic VSV virus comprising one or more changes in nucleic acid sequence resulting in substitution of the serine at codon 126 of SEQ ID NO. 3, with an amino acid selected from the group consisting of alanine (A), arginine (R), asparagine (N), aspartic acid (D), cysteine (C), glutamine (Q), glutamic acid (E), glycine (G), histidine (H), isoleucine (I), leucine (L), lysine (K), methionine (M), phenylalanine (F), proline (P), tryptophan (W), or valine (V) and substitution of aspartic acid (D) at codon 223 of SEQ ID NO. 5 with an amino acid selected from the group consisting of serine (S), threonine (T), or tyrosine (Y).
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3. An isolated oncolytic VSV virus with SEQ ID NO:
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Specification