Method for detecting replication or colonization of a biological therapeutic
Inventors
Szalay, Aladar A. • Stritzker, Jochen • Hess, Michael
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8859256-B2
Publication Date
2014-10-14
Expiration Date
Abstract
Methods for detecting replication in or colonization of a host by a biological therapeutic, such as an oncolytic virus, cells administered for cell therapy and gene therapy vectors, are provided. In the methods, a product produced by the biological therapeutic is detected in a sample of tissue or body fluid distinct from the administered therapy or locus thereof, thereby permitting assessment of the therapy and/or monitoring its progress.
Core Innovation
The invention provides a method for treating cancer and monitoring therapeutic progress in a subject having tumors by administering an oncolytic virus encoding a β-glucuronidase. The oncolytic virus targets and treats cancer, and β-glucuronidase activity indicates oncolytic viral colonization or replication in the cancer.
Monitoring is performed using a sample obtained from the subject that is a body fluid or tissue sample that is not a tumor sample. β-glucuronidase activity in the non-tumor sample is detected by adding a substrate for β-glucuronidase and determining the presence of a product catalyzed by the reaction of β-glucuronidase with the substrate.
The detection of the product indicates that the oncolytic virus has colonized or is replicating in tumor tissue or a tumor cell in the subject and that the oncolytic viral therapy is treating the tumor tissue or cell. The detection result is used to guide continued oncolytic viral therapy and to monitor therapeutic efficacy without requiring tumor-sample analysis.
Claims Coverage
The independent claim covers one combined treatment-and-monitoring method with four inventive features: oncolytic virus administration encoding β-glucuronidase, non-tumor sample collection, substrate-based detection of β-glucuronidase activity, and use of the detection result to indicate tumor-associated colonization or replication and support continued therapy. Dependent claims refine β-glucuronidase sequence identity, sample timing, permitted non-tumor body fluid types, and substrate selection.
Oncolytic virus encoding β-glucuronidase for cancer treatment with activity indicating colonization or replication
Administering to the subject an oncolytic virus encoding a β-glucuronidase, wherein the oncolytic virus targets and treats cancer and the β-glucuronidase activity indicates oncolytic viral colonization or replication in the cancer.
Non-tumor sample collection for monitoring
Obtaining a sample from a subject, wherein the sample is a body fluid or tissue sample that is not a tumor sample.
Substrate-based detection of β-glucuronidase activity in a non-tumor sample
Detecting β-glucuronidase activity in the sample by the addition of a substrate for β-glucuronidase.
Determining a substrate reaction product to indicate tumor tissue or cell colonization or replication
Determining the presence of a product catalyzed by the reaction of the β-glucuronidase with the substrate, wherein the detection of the product indicates that the oncolytic virus has colonized or is replicating in a tumor tissue or cell and is treating the tumor tissue or cell, and oncolytic viral therapy be continued.
Selecting the oncolytic virus from named virus types
Select the oncolytic virus from named virus types including poxvirus, adenovirus, reovirus, herpes virus, adeno-associated virus, lentivirus, retrovirus, rhabdovirus, papillomavirus, vesicular stomatitis virus, measles virus, Newcastle disease virus, picornavirus, sindbis virus, parvovirus, coxackievirus, influenza virus, mumps virus, poliovirus, or semliki forest virus.
β-glucuronidase sequence defined by SEQ ID NO:121 identity or catalytically active portion
Use β-glucuronidase having either the amino acid sequence of SEQ ID NO:121, a catalytically active portion thereof, or an amino acid sequence with at least 85% sequence identity to the amino acid sequence set forth in SEQ ID NO:121.
Substrate selection for β-glucuronidase detection using enumerated glucuronide options
Use a substrate selected from enumerated glucuronide compounds and their pharmaceutically acceptable salts for β-glucuronidase detection.
Permitted non-tumor sample type selected from body fluids and excretions
Use a sample that is a selected body fluid chosen from a specified list of different bodily fluids and excretions including serum and urine among others.
Sample timing window after treatment for obtaining the non-tumor sample
Collect the sample between about 12 hours and 1 month after treatment with the oncolytic virus.
The claim scope centers on using an oncolytic virus encoding β-glucuronidase for cancer treatment, then detecting β-glucuronidase activity in a non-tumor body fluid or tissue sample via a β-glucuronidase substrate reaction product. When the product is detected, it indicates tumor-associated oncolytic viral colonization or replication and supports continuing the oncolytic viral therapy. Dependent claims further refine β-glucuronidase sequence identity and enumerate β-glucuronidase substrates and permissible non-tumor sample types, with a collection time window.
Stated Advantages
Provides non-invasive monitoring of therapeutic progress using body fluid or tissue samples that are not tumor samples.
Links detected β-glucuronidase substrate reaction products to oncolytic viral colonization or replication in tumor tissue or cells, supporting continued therapy.
Enables monitoring of therapeutic efficacy without requiring tumor-sample analysis.
Documented Applications
Treating cancer in a subject having tumors using an oncolytic virus encoding β-glucuronidase and monitoring therapeutic progress via detection of β-glucuronidase activity in a non-tumor body fluid or tissue sample.
Monitoring oncolytic viral colonization or replication in tumor tissue or cells using non-tumor body fluid or tissue samples and a β-glucuronidase substrate reaction product.
Interested in licensing this patent?