Attenuated reovirus

A method of treating a cancer in a subject comprising the cancer, the method comprising administering intratumorally (a) an effective amount of an attenuated reovirus comprising at least one mutation in a wild type gene selected from wild type S1 and wild type S4 wherein the wild type S1 gene comprises one of the nucleotide sequences of SEQ IDS NO:

• 1, 3, 7, 9 and 10, and the wild type S4 gene comprises one of the nucleotide sequences of SEQ ID NOS:
• 13 and 14, or (b) a malignant cell(s) isolated from the cancer wherein the malignant cell(s) are contacted with an effective amount of the attenuated reovirus ex vivo
• (A) the S1 mutations are selected from;
• (a) a mutation that encodes a premature stop codon at codon 9 of one of the amino acid sequences of SEQ ID NOs:7 or 9 or 10;
• (b) a mutation at a nucleotide that leads to a substitution of leucine to proline at codon 116 of one of the amino acid sequences of SEQ ID NOs:7 or 9 or 10;
• (c) a mutation at a nucleotide that leads to a substitution of valine to alanine at codon 127 of one of the amino acid sequences of SEQ ID NOs:7 or 9 or 10;
• (d) a mutation at a nucleotide that leads to insertion of a stop codon at codon 251 of one of the amino acid sequences encoded by SEQ ID NOs:7 or 9 or 10;
• and
• (e) a mutation at a nucleotide that leads to a substitution of isoleucine to methionine at codon 300 of one of the amino acid sequences of SEQ ID NOs:7 or 9 or 10;
• and
• (B) wherein the S4 mutations are selected from;
• (a) a substitution of C to T at nucleotide 562 of the nucleotide sequence of SEQ ID NO:
• 13 or 14;
• and
• (b) a substitution of A to T at nucleotide 784 of the nucleotide sequence of SEQ ID NO:
• 13 or 14.