Advertisement

Topics

Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin Domains Lacking Both T-cell and B-cell Epitopes

19:00 EST 7 Feb 2012 | NIH

Immunotoxins can kill cancer cells while allowing healthy, essential cells to survive. As a result, patients receiving an immunotoxin are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins often leads to a reduced patient response due to the formation of neutralizing antibodies against immunogenic B-cell and T-cell epitopes contained within PE. To improve the therapeutic effectiveness of PE-containing immunotoxins through multiple rounds of drug administration, NIH inventors have sought to remove the B-cell and T-cell epitopes within PE. Previous work demonstrated that the removal of the major B-cell epitopes from PE reduced the immunogenicity of PE. This technology involves the identification of major T-cell epitopes on PE, and the removal of the primary T-cell epitope by mutation or deletion. By combining the T-cell epitope mutations with modifications that remove B-cell epitopes, it is possible to create PE-based immunotoxins that have even greater resistance to the formation of neutralizing antibodies. Immunotoxins containing these new PE-variants are expected to have improved therapeutic efficacy.

IC: 
NCI
NIH Ref. No.: 
E-174-2011/0
TAB No: 
TAB-2361
Advantages: 
  • PE variants now include the removal of both B-cell and T-cell epitopes, further reducing the formation of neutralizing antibodies against immunotoxins which contain the PE variants
  • Less immunogenic immunotoxins result in improved therapeutic efficacy by permitting multiple rounds of administration
  • Targeted therapy decreases non-specific killing of healthy, essential cells, resulting in fewer non-specific side-effects and healthier patients
Applications: 
  • Essential component of immunotoxins
  • Treatment of any disease associated with increased or preferential expression a specific cell surface receptor
  • Specific diseases include hematological cancers, lung cancer, ovarian cancer, breast cancer, and head and neck cancers
Development Status: 

Pre-clinical

Provider Technology ID: 
2361
Updated On: 
Sep 6, 2017
Date Published: 
Wednesday, February 8, 2012
Provider Classifications: 
Publications: 
Patent Application: 
15/095,470
61/495,085
PCT/US2012/041234
14/123,971
15/693,705
Patent Authority: 
US
US
PCT
US
US
2016-04-21 00:00:00
2016-04-21 00:00:00
Patent Number: 
9,346,859
Licensing Contacts: 
LPM Address: 
  --
United States
Lead Inventor: 
Inventor IC: 
NCI
Inventor Lab URL: 
http://irp.nih.gov/pi/ira-pastan
LPM FIrst Name: 
David
LPM Last Name: 
Lambertson
LPM Address: 
9609 Medical Center Drive, Room 1E-530 (MSC 9702)
LPM City: 
Rockville
LPM Zip: 
20850-9702
Inv Is lead: 
LPM State: 
MD
LPM Phone: 
240-276-6467
LPM Suffix: 
Ph.D.
LPM Organization: 
NIH Office of Technology Transfer
LPM Fax: 
240-276-5504
DTDT Classification: 
Cancer
Therapeutics
Immunoconjugates
Toxins
DTDT Description: 
Cancer
Cancer - Therapeutics
Cancer - Therapeutics - Immunoconjugates
Cancer - Therapeutics - Immunoconjugates: Toxins
Pat Filing Date: 
2016-04-11
2011-06-09
2012-06-07
2013-12-05
2017-09-01
Patent Issue Date: 
2016-05-24
Disease Area Term: 
Collaboration Sought: 
Yes
Institute or Center: 
Related Patents: 
8,936,792
8,871,906
8,907,060
7,081,518
Related Patent Publish Date: 
1340600400
1220504400
1284094800
927781200
1153803600
1006236000
1122613200
1153803600
1188882000
1220504400
1252645200
959317200
Related Patent Application: 

13/395,422

12/676,203

PCT/US2010/048504

60/160,071

11/997,202

09/979,539

60/703,798

PCT/US2006/028986

60/969,929

PCT/US2008/075296

61/241,620

PCT/US00/14829

Related Patent Authority: 
US
US
PCT
US
US
US
US
PCT
US
PCT
US
PCT
Related Invention: 
E-139-1999/0
E-262-2005/0
E-292-2007/0
E-269-2009/0
E Number Only: 
E-174-2011
Inventor First Name: 
Ira
Inventor Last Name: 
Pastan

Original Article: Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin Domains Lacking Both T-cell and B-cell Epitopes

NEXT ARTICLE

More From BioPortfolio on "Increased Therapeutic Effectiveness of Immunotoxins That Use Toxin Domains Lacking Both T-cell and B-cell Epitopes"

Quick Search
Advertisement
 

Relevant Topics

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Antibodies
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...