Advertisement

Topics

Extracellular Vesicles, Methods of Making Them, and Methods of Reducing Liver Uptake of Extracellular Vesicles

20:00 EDT 27 Jun 2017 | NIH

Extracellular vesicles (EVs) are an emerging new class of nano-sized biological delivery systems involved in intercellular communication, immune responses, and tissue regeneration, that are increasingly being investigated for therapeutic potential. Since EVs are released by cells endogenously and naturally transfer genetic material and proteins, they offer a safer alternative for delivery of biologicals (e.g. RNAs, cytokines, monoclonal antibodies). In addition, EVs carry complex biological messages of the parental cell, and thus are being tested as safer alternatives to cell therapy (e.g. in lieu of mesenchymal stem cell therapy for heart tissue regeneration). Furthermore, in human clinical trials EVs have been used as cancer vaccines and for immunomodulation.

Significant opportunity for EV discovery and understanding remain. For the successful translational development of EVs there is a need for efficient, scalable processes for production, therapeutic enhancement, and purification. In addition to being scalable, these methods must retain the biological properties of EVs to avoid loss of their therapeutic activity. There are also opportunities to improve the use of EVs to treat disease. Administered EVs are rapidly cleared by the reticuloendothelial system (RES), especially by liver macrophages. The clearance of EVs by the RES decreases their delivery to desired target sites, including tumors. Consequently, there is a need for improved EVs, methods of producing EVs, and methods of improving delivery of EVs to a target site.

Researchers at the National Cancer Institute (NCI) have developed a method of scalable EV production and effective delivery, thereby representing a significant market opportunity. The NCI’s technology provides a fully scalable procedure for production and purification of extracellular vesicles enriched for hetIL-15, a molecule in clinical trials for treatment of metastatic cancer. The technology includes a novel, bioactive, fully human form of the cytokine (hetIL-15/Lactadherin) capable of more efficiently coating the surface of EVs. The invention also includes methods for producing large amounts of these EVs in a bioreactor, and ways of efficiently obtaining highly purified EV preparations using cGMP-compatible tools (namely, tangential flow filtration and size-exclusion chromatography). Moreover, the invention includes methods of blocking the rapid clearance of administered EVs by liver macrophages, which enables enhanced accumulation of EVs carrying the therapeutic molecule, hetIL-15 to tumors. Implementation of the NCI’s methods will allow interested commercial partners to proceed with large-scale production of EVs for therapeutic use. Additionally, commercial partners may expand on the scope of the invention, for example by developing more effective molecules for blocking liver uptake and using the hetIL-15/Lactadherin protein to coat EVs from primary human cells.

IC: 
NCI
NIH Ref. No.: 
E-083-2016/0
Advantages: 
  • 60 times higher EV yield per mL cell culture vs. conventional methods
  • 55 times more loading of bioactive hetIL-15 on EVs
  • 4-5 times less clearance of EV by liver macrophages, and a corresponding increased delivery of EVs to tumors
Applications: 
  • cGMP-compatible, large-scale purification of EVs from cultured primary cells and cell lines for pre-clinical and clinical development
  • Development of therapeutic EVs enriched for bioactive hetIL-15, using EVs from primary human cells or recombinant cell lines
  • Development of novel molecules that block scavenger receptors, in order to modulate uptake of therapeutic EVs by liver macrophages and enhance targeted EV delivery
Provider Technology ID: 
3140
Updated On: 
Jun 28, 2017
Date Published: 
Wednesday, June 28, 2017
Provider Classifications: 
Publications: 
Patent Application: 
62/316,276
PCT/US2017/025550
Patent Authority: 
US
PCT
Licensing Contacts: 
Lead Inventor: 
Inventor IC: 
NCI
NCI
NCI
NCI
Bilkent University
Inventor Lab URL: 
http://irp.nih.gov/pi/george-pavlakis
http://irp.nih.gov/pi/barbara-felber
LPM FIrst Name: 
Rose
LPM Last Name: 
Freel
LPM Address: 
8490 Progress Drive, Riverside 5, Suite 400
LPM City: 
Frederick
Inv Is lead: 
LPM Zip: 
21701
LPM State: 
MD
LPM Phone: 
301-624-1257
LPM Suffix: 
Ph.D.
LPM Organization: 
NIH Office of Technology Transfer
LPM Fax: 
301-631-3027
DTDT Classification: 
Cancer
Vaccine
DTDT Description: 
Cancer
Vaccine
Pat Filing Date: 
2016-03-31
2017-03-31
Publication Link: 
https://www.ncbi.nlm.nih.gov/pubmed/27522254
Publication Caption: 
PMID 27522254
Publication Title: 

Watson DC, et al.

Application Term: 
Disease Area Term: 
Technology Term: 
Collaboration Sought: 
Yes
Institute or Center: 
Collaboration Opportunity: 

Researchers at the NCI seek licensing and/or co-development research collaborations for isolated or purified Extracellular Vesicles (EVs), a method of preparing isolated or purified EVs containing a therapeutic protein, for example, hetIL-15/Lactadherin fusion, methods of reducing liver uptake of EVs, methods of improving delivery of EVs to a target site, and methods of treating or preventing cancer by administering the isolated or purified EVs.

Related Patent Publish Date: 
1182920400
1214542800
1260856800
1486101600
1382504400
1429246800
Related Patent Application: 

60/937,471

PCT/US2008/008084

12/666,052

15/424,621

PCT/US2013/066424

14/436,523

Related Patent Authority: 
US
PCT
US
US
PCT
US
Related Invention: 
E-141-2008/0
E-054-2013/2
E Number Only: 
E-083-2016
Inventor First Name: 
George
Barbara
Dionysios
Define
Ihsan
Inventor Last Name: 
Pavlakis
Felber
Watson
Bayik
Gursel

Original Article: Extracellular Vesicles, Methods of Making Them, and Methods of Reducing Liver Uptake of Extracellular Vesicles

NEXT ARTICLE

More From BioPortfolio on "Extracellular Vesicles, Methods of Making Them, and Methods of Reducing Liver Uptake of Extracellular Vesicles"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Monoclonal antibodies MAbs
Monoclonal antibodies recognise and attach to specific proteins produced by cells.  Types of monoclonal antibodies used to treat cancer cells: Block cell dividing dividing signals Transport cancer drugs or radiation to cancer cells Tr...