Salk Institute

Technologies Available for Licensing

Rapid Generation of Customized Tumor-Selective Oncolytic Adenoviruses

Allows for the efficient optimization of viruses for use in oncolytic viral therapies.

INVENTION: The goal of oncolytic viral therapy is to specifically infect and kill tumor cells without causing damage to normal cells. Although adenovirus is one of the most commonly used gene transfer vectors in basic and pre-clinical research, their potential as effective oncolytic viruses has been greatly limited by the reliance on the common serotypes Ad2 and Ad5 and the technical difficulties associated with the manipulation of the large 36kb viral genomes. In addition, pre-existing neutralizing antibodies against Ad2/Ad5, off-target liver uptake and inflammation, and the absence of true tumor-specific replication have limited the use of these viruses in the clinic. Researchers at the Salk Institute have developed a novel platform for the rapid assembly of oncolytic adenoviral vectors from libraries of component parts. The functions and diversity of the genomic parts is provided by previously reported mutations, directed evolution approaches based on structure, heterologous elements and disparate adenovirus serotypes, mutants and species. This assembly method allows for the rapid generation of custom adenoviruses with the desired target and/or replication specificity, lytic properties, and the ability to escape the host immune system or induce a favorable tumor-specific immune response.

Investigators used this assembly method to systematically engineer oncolytic adenoviruses that only replicate and therefore kill cells, which have defects in either the p53 or Rb pathway respectively. The p53 and Rb tumor suppressor pathways are mutated in almost all human cancers. These very same cellular controls are targeted and disabled by adenoviral-encoded proteins to allow for their replication. Salk researchers exploited this characteristic of adenoviruses to generate replication selective oncolytic adenoviruses. The viruses were able to infect, replicate and kill their respective target cancer cells without deleterious effects on normal cells.

This new assembly platform holds great promise for advancing the development of new oncolytic viruses. The ability to efficiently optimize viruses for use in oncolytic viral therapies will facilitate the development of viruses that not only specifically target and kill cancer cells, but that can avoid liver toxicity, evade neutralizing antibodies and reactivate beneficial host antitumor immune responses.

APPLICATIONS:

  • Development of oncolytic viral therapies

ADVANTAGES

  • Ability to manipulate the 36kb viral genome rapidly and systematically
  • Library-based
  • Can target nearly any cell type or tissue type
  • Ability to combine parts of viral genomes from various serotypes
  • Can generate human/mouse chimeras for use in genetically engineered mouse models of cancer (GEMMs)
  • Can generate novel adenoviruses that can evade neutralizing antibodies produced to Ad2/5 adenoviruses
  • Efficient expression and delivery of multi-protein complexes and entire pathways
  • Allows for generation of either replication-defective or replication-competent virus

BACKGROUND: Cancer is a diverse group of diseases characterized by uncontrolled cell growth and is responsible for approximately 8 million deaths worldwide each year. Current therapies, including surgery, chemotherapy and radiotherapy, although effective, often have serious side effects and are frequently ineffective at eliminating all malignant cells. Oncolytic viral therapy holds great promise for a more targeted and effective treatment without the deleterious side effects associated with standard therapies.   
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INVENTORS: Clodagh O'Shea and Colin Powers 
PATENT STATUS: US Patent Appl No. 2013/0231267, Australia, Brazil, Canada, China, Europe, India, Japan, Korea
PUBLICATION: In preparation
INVENTORS: Clodagh O'Shea and Colin Powers 
PATENT STATUS: US Patent Appl No. 2013/0243729, Australia, Brazil, Canada, China, Europe, India, Japan, Korea
PUBLICATION: In preparation
INVENTORS: Clodagh O'Shea and Shigeki Miyaki-Stoner 
PATENT STATUS: US Provisional Application Filed
PUBLICATION: In preparation
CONTACT: Michelle A. Booden, Ph.D., 858.453.4100 x1612, mbooden@salk.edu
REFERENCE #: S10004, S10005, S13002
Patent Information:
Category(s):
Oncology
For Information, Contact:
Michelle Booden
Director, Licensing and Intellectual Property
Salk Institute
mbooden@salk.edu
Inventors:
Keywords:
Adenovirus
Cancer Therapeutics
Cancer Vaccines
Oncology
Oncolytic Therapy
O'Shea
Personalized Medicine
Proliferative disorders
Synthetic Biology
Tumors
Vaccine
Viral Vectors
Virus
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