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Monoclonal Antibodies and Immunoconjugates Directed to the Non-ShedPortion (“Stalk”) of Mesothelin are Excellent Candidates for Developing Therapeutic Agents

20:00 EDT 25 Apr 2019 | NIH

Human mesothelin is overexpressed by various cancers such as synovial sarcoma, mesothelioma, and ovarian, lung, esophageal, and gastric cancers. This selective expression on certain cancers suggests that mesothelin is an excellent target for anticancer therapeutics. However, a large fragment (“the shed portion”) of mesothelin is constantly shed from cells, and all current anti-mesothelin antibodies bind to the shed portion. As a result, the therapeutic efficacy of these antibodies has been low because they are unable to exert their therapeutic effect on the cell before their binding region is shed.

Fortunately, a piece (“the stalk”) of mesothelin remains attached to the cell surface after shedding.  Since antibodies to the stalk would remain bound to diseased cells, they can be more effective in killing cancer cells than currently available anti-mesothelin antibodies. Scientists at the National Cancer Institute (NCI) have invented antibodies that specifically recognize and bind to the stalk of human mesothelin with high affinity.  These antibodies represent excellent candidates for development of therapeutic agents and are available for licensing and/or co-development opportunities.

IC: 
NCI
NIH Ref. No.: 
E-106-2017
Advantages: 
  • This is the only antibody that binds to the stalk portion of mesothelin, allowing the antibody to remain attached to the cell to exert a therapeutic effect
  • Specific binding to cancer cells allows selective killing, potentially limiting drug side effects and improving patient quality of life
Applications: 
  • Therapeutic Uses
    • As an unconjugated antibody
    • As a targeting moiety for CARs, antibody-drug conjugates (ADC), immunotoxins, bispecific antibodies, etc.
  • Diagnostic agent for detection and monitoring levels of mesothelin-expressing cancer cells
Development Status: 

Pre-clinical (in vivo)

Updated On: 
Apr 26, 2019
Date Published: 
Friday, April 26, 2019
Patent Application: 
PCT/US2018/033236
Lead Inventor: 
Inventor IC: 
NCI
NCI
Inventor Lab URL: 
https://ccr.cancer.gov/Laboratory-of-Molecular-Biology/ira-pastan
https://ccr.cancer.gov/Laboratory-of-Molecular-Biology/mitchell-ho
LPM FIrst Name: 
John
LPM Last Name: 
Hewes
Inv Is lead: 
LPM Phone: 
240-276-5515
LPM Suffix: 
Ph.D.
LPM Organization: 
NCI - National Cancer Institute
DTDT Classification: 
Therapeutics
DTDT Description: 
Therapeutics
Patent Issue Date: 
2018-05-17
Publication Link: 
https://www.ncbi.nlm.nih.gov/pubmed/27196771
Publication Caption: 
PMID 27196771
Publication Title: 

Awuah et al., Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins.

Collaboration Sought: 
Yes
Institute or Center: 
Collaboration Opportunity: 

Licensing and research collaboration

Related Invention: 
E-262-2005
E-292-2007
E Number Only: 
E-106-2017
Inventor First Name: 
Ira
Masanori
Tapan
Mitchell
Inventor Last Name: 
Pastan
Onda
Bera
Ho

Original Article: Monoclonal Antibodies and Immunoconjugates Directed to the Non-ShedPortion (“Stalk”) of Mesothelin are Excellent Candidates for Developing Therapeutic Agents

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