Methods for assessing effectiveness and monitoring oncolytic virus treatment
First Claim
1. A method for testing for or monitoring efficacy of treatment with an oncolytic virus for treatment of solid tumors, other cancers and metastatic diseases, comprising testing a body fluid sample obtained from a subject to whom an oncolytic reporter virus has been administered to identify any tumor cells that circulate in the body fluid by detecting the oncolytic reporter virus in tumor cells the sample, wherein:
- testing is performed at a pre-determined time following administration of the virus, wherein the predetermined time is a time sufficient for the virus to infect a tumor cell in the subject, but before efficacious therapy would shrink tumors or eliminate any circulating tumor cells (CTCs); and
detection of the reporter virus in tumor cells in the body fluid sample is indicative that the treatment with the oncolytic virus is or will be efficacious.
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Abstract
Diagnostic methods for in vivo and ex vivo detection of circulating tumor cells (CTCs) for the diagnosis and treatment of cancer are provided. The diagnostic methods employ oncolytic viruses alone or in combination with one or more tumor cell enrichment and/or detection methods. Combinations and kits for use in the practicing the methods also are provided.
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Citations
66 Claims
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1. A method for testing for or monitoring efficacy of treatment with an oncolytic virus for treatment of solid tumors, other cancers and metastatic diseases, comprising testing a body fluid sample obtained from a subject to whom an oncolytic reporter virus has been administered to identify any tumor cells that circulate in the body fluid by detecting the oncolytic reporter virus in tumor cells the sample, wherein:
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testing is performed at a pre-determined time following administration of the virus, wherein the predetermined time is a time sufficient for the virus to infect a tumor cell in the subject, but before efficacious therapy would shrink tumors or eliminate any circulating tumor cells (CTCs); and detection of the reporter virus in tumor cells in the body fluid sample is indicative that the treatment with the oncolytic virus is or will be efficacious. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 51, 52)
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50. The method of any of claim 50, wherein the antibody specifically binds to a polypeptide that comprises the sequence NDSSRAPSSGMDAS (SEQ ID NO:
- 53) or an epitope therein.
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53. A method of detecting a viable tumor cells in a body fluid sample, comprising:
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a) enriching tumor cells in a body fluid sample from a subject administered an oncolytic reporter virus to produce an enriched sample; and b) detecting the reporter virus in tumor cells in the sample, thereby detecting viable tumor cells in the sample.
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54. A method of detecting a tumor cell in a body fluid sample, comprising testing a body fluid sample from a subject, wherein the subject has not been treated with an oncolytic reporter virus, the method comprising:
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a) enriching tumor cells from the sample to produce an enriched sample; b) contacting tumor cells from the sample with an oncolytic reporter virus; and c) detecting the oncolytic reporter virus, thereby detecting tumor cells in the sample. - View Dependent Claims (55, 56)
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57. A method for detecting viable circulating tumor cells, comprising:
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a) detecting tumor cells in a body fluid sample that is infected with an oncolytic reporter virus, wherein; the sample is obtained from a subject who has been administered an oncolytic reporter virus; and the tumor cells are detected by detecting a tumor cell marker; b) optionally enriching tumor cells in the sample to produce an enriched sample; and
thenc) detecting tumor cells with the tumor cell marker that are infected with the virus by detecting the oncolytic reporter virus, whereby detection of infected tumor cells effects detection of viable circulating tumor cells. - View Dependent Claims (58, 59, 60)
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61. A method of assessing prognosis of a cancer, comprising testing a body fluid sample from a subject by:
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a) enriching tumor cells in the sample to produce an enriched sample; b) contacting the sample or enriched sample or cells from the same with an oncolytic reporter virus; and c) identifying cancer stem cells by; i) detecting the oncolytic reporter virus to identify cells infected with the virus and from the identified cells identifying stem cells;
orii) identifying stem cells and from among the identified stem cells identifying cells infected with virus, whereby the presence of cancer stem cells is indicative of the presence of an aggressive cancer. - View Dependent Claims (62)
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63. An antibody that specifically binds to the extracellular domain of NIS that is expressed in cell, wherein the NIS protein is encoded by an oncolytic virus that has infected the cells that express the NIS protein.
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64. An isolated polypeptide, comprising the sequence NDSSRAPSSGMDAS (SEQ ID NO:
- 53), wherein the polypeptide does not comprise the complete extracellular domain of NIS.
- View Dependent Claims (66)
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65. An antibody that specifically binds to the polypeptide of claim 65, and also binds to an epitope on the extracellular domain of NIS when expressed on the surface of a cell.
Specification