Salk Institute

Technologies Available for Licensing

Adenoviral Tumor Diagnostics

Diagnostic viral reporters to define the malignant phenotype of tumors, and functionally determine their ability to respond to different therapies.  

INVENTION: Genome sequencing has accelerated our understanding of how molecular alterations determine a tumor's response to targeted drugs, ultimately leading to the development of a number of personalized therapies. However, a number of challenges remain, including tumor heterogeneity, polygenic drug resistance and the need for more predictive prognostic markers. Dr. O'Shea is developing a powerful diagnostic solution that detects circulating tumor cells (CTCs) from a blood biopsy using viral labeling, and can sort and array those cells based on pathway-specific viruses. These viruses can then be used to define the malignant phenotype of the cells, and functionally determine their ability to respond to different therapies. This approach will not only facilitate repeat analysis, but also potentially capture a wider picture of the multiple primary and metastatic clones in the tumors, quantifying their malignant potential and facilitating the identification 'up-front' of therapies that are most effective in ablating an individual patient's tumor. 

This is a powerful technique to identify therapeutic targets associated with specific pre-selected cancer types, to identify the correct therapeutic approach for individual patients and to stratify patients in clinical testing, ultimately accelerating the development of designer therapeutics.

APPLICATIONS:

  • Precision Medicine in Cancer
  • Personalizing therapies to patients
  • Development of targeted therapies
  • Identification of therapeutic targets specific to selected tumor types
  • Phenotypic interrogation of the defective pathways in circulating tumor cells, tissue samples and other material

ADVANTAGES 

  • Rapid, customizable diagnostic platform
  • Ability to interrogate the malignant PHENOTYPE of cells- not just the genotype
  • Generates a wider picture of multiple primary tumor clones than traditional genotyping
  • Can ID specific mutants 
  • Technology discriminates live cells from dead cells, which can’t be done with EPCAM Ab 
  • Provides for simple sample collection, and repeat analysis
  • Efficient assembly of viral reporters to probe multiple transcriptional and molecular markers simultaneously
  • Ability to manipulate the 36kb viral genome rapidly and systematically
  • Orthogonal approach to personalized medicine- integrate genomic analysis, activity, develop personalized therapeutic, patho-physiologic  outcome measures 

STAGE OF DEVELOPMENT:  Developed at laboratory scale, and tested in patient samples. Ready for scale-up.

BACKGROUND: This diagnostic solution has been made possible through the development of a modular adenovirus assembly platform. This platform facilitates the creation of diagnostic viruses that incorporate multiple transcriptional and molecular modules in their genomes to infect and phenotype a patient's CTCs. Using these viral reporters, the molecular lesions and malignant characteristics of any given CTC will be rapidly discerned (within 24 hours) and scored via a standardized automated platform. To date,  A major challenge with viral construction has been the ability to manipulate large genomes in order to engineer particles with the desired properties. Dr. O'Shea's approach divides the adenoviral genome into 4 modules based on evolutionary conserved sequences and functions. Different combinations of these modules derived from both synthetic and natural sources, can be rapidly combined using multi-site in vitro recombination, to create recombinant viruses with desired properties. 
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INVENTORS: Clodagh O'Shea and Colin Powers
PATENT STATUS: PCT Patent Appl No. PCT/US2013/031646
CONTACT: Michelle A. Booden, Ph.D., 858.453.4100 x1612, mbooden@salk.edu
REFERENCE #: S12002
Patent Information:
For Information, Contact:
Michelle Booden
Director, Licensing and Intellectual Property
Salk Institute
mbooden@salk.edu
Inventors:
Keywords:
Adenovirus
Cancer Diagnostics
Circulating Tumor Cells
Diagnostic
DNA Virus
Oncology
O'Shea
Personalized Medicine
Synthetic Biology
Tumors
Viral Reporters
Virus
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