Oncolytic viruses and methods for treating neoplastic disorders

摘要

The disclosure provides mutant ribonucleotide reductase strains of poxviruses including for example vaccinia viruses. The disclosure also provides methods and for the use of these mutant ribonucleotide reductase strains of vaccinia viruses in oncolytic virotherapy. Also provided in the disclosure are vector constructs for generating mutant ribonucleotide reductase strains of poxviruses including for example vaccinia viruses. The disclosure also provides poxviruses comprising a functionally inactivated R2 gene.

主权项

1. A method for inducing cell death in a neoplastic disorder cell, the method comprising:
contacting said cell with an effective amount of a vaccinia virus comprising a gene encoding a modified R2 protein comprising an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 1, wherein vaccinia virus does not express a wild type R2 protein; and
wherein the modified R2 protein expressed by the vaccinia virus comprises a substitution of a tyrosine residue, wherein the substituted tyrosine residue corresponds to position 300 of SEQ ID NO: 1, orwherein the modified R2 protein expressed by the vaccinia virus comprises a deletion of 7 amino acids of R1 binding domain (R1BD); andwherein said contacting is effective to induce cell death in the neoplastic disorder cell, wherein the neoplastic disorder cell expresses ribonucleotide reductase.