Oncolytic viruses as phenotyping agents for neoplasms
First Claim
1. A method of diagnosing a neoplasm in an animal by phenotype, comprising:
- (a) providing a biological sample from the animal, wherein the sample comprises neoplastic cells with one or more unknown phenotypes;
(b) providing at least two oncolytic viruses, wherein each oncolytic virus selectively replicates in neoplastic cells having a known phenotype selected from the group consisting of ras pathway activation, interferon-resistance, p53-deficiency and Rb-deficiency; and
wherein each of the at least two oncolytic viruses replicates in neoplastic cells having a known different phenotype;
(c) contacting the neoplastic cells from the sample with each of the at least two oncolytic viruses under conditions which allow each oncolytic virus to selectively replicate in the neoplastic cells from the sample;
(d) determining if each of the oncolytic viruses selectively replicates in the neoplastic cells from the sample; and
(e) diagnosing a neoplasm in the animal as comprising cells of a known phenotype according to the ability of each of the oncolytic viruses to selectively replicate in the neoplastic cells from the sample.
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Abstract
The present invention provides a method of diagnosing neoplasms having a particular phenotype by using oncolytic viruses that selectively replicate in neoplasms having the particular phenotype. For example, reovirus does not replicate in normal cells. However, reovirus selectively replicate in cells with an activated ras pathway, which leads to death of these cells. Therefore, a cell which becomes neoplastic due to, at least in part, elevated ras pathway activities can be diagnosed by its susceptibility to reovirus replication. This invention can further be applied, using other oncolytic viruses, to the diagnosis and/or treatment of other tumors, such as interferon-sensitive tumors, p53-deficient tumors and Rb-deficient tumors. Kits useful in the diagnosis or treatment disclosed herein are also provided.
26 Citations
10 Claims
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1. A method of diagnosing a neoplasm in an animal by phenotype, comprising:
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(a) providing a biological sample from the animal, wherein the sample comprises neoplastic cells with one or more unknown phenotypes; (b) providing at least two oncolytic viruses, wherein each oncolytic virus selectively replicates in neoplastic cells having a known phenotype selected from the group consisting of ras pathway activation, interferon-resistance, p53-deficiency and Rb-deficiency; and
wherein each of the at least two oncolytic viruses replicates in neoplastic cells having a known different phenotype;(c) contacting the neoplastic cells from the sample with each of the at least two oncolytic viruses under conditions which allow each oncolytic virus to selectively replicate in the neoplastic cells from the sample; (d) determining if each of the oncolytic viruses selectively replicates in the neoplastic cells from the sample; and (e) diagnosing a neoplasm in the animal as comprising cells of a known phenotype according to the ability of each of the oncolytic viruses to selectively replicate in the neoplastic cells from the sample. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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Specification