Human Monoclonal Antibody Against Mesothelin

Background:
The National Cancer Institute's Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize human antibodies that act against mesothelin.

NIH inventors have demonstrated in pre-clinical experiments an anti-mesothelin antibody of human origin that is an attractive alternative to the murine anti-mesothelin antibodies currently available. The antibody has the ability to efficiently recognize mesothelin on the surface of cells, and induce antibody-dependent cell-mediated cytotoxicity (ADCC) in mesothelin-positive cells.

Technology:
Mesothelin is a cell surface protein that is naturally expressed at very low levels, but that is significantly increased in aggressive tumors such as mesotheliomas, and pancreatic and ovarian tumors. Therefore, mesothelin is an excellent candidate for tumor-targeted immunotherapeutics. However, the only antibodies against mesothelin that are currently available for clinical trials are of murine origin. The use of these antibodies may be limited by their potential to elicit adverse immune responses in patients with repeated doses.

The anti-mesothelin antibody has potential use as a cancer therapeutic and diagnostic for mesotheliomas, and pancreatic and ovarian tumors, and for diagnosis and monitoring of mesothelin-positive tumors. Additionally, the antibody may be used as a research agent for the detection of mesothelin. Because this antibody is fully human, the probability for immune responses and side effects is lower than that of murine, chimeric, and humanized antibodies.

R&D Status:
This antibody was converted to an IgG1 format. It binds to cells expressing mesothelin and mediate ADCC in vitro. Studies in animal models are being planned.

Further R&D Needed:

• Develop a cell line for large scale production and test it in animal models of cancer
• Conjugate antibody with various cancer drugs and drug-loaded nanoliposomes for targeted delivery
• Reformat antibody as a nanoantibody for better penetration in solid tumors
• Perform combination tests with antibodies that have been approved for treatment

IP Status:
U.S. Provisional Application filed 27 Mar 2008

Value Proposition:
Currently there is a chimeric mesothelin antibody in phase I trial. Our mesothelin antibody is fully-human and with high affinity. May have reduced immunogenicity, thereby allowing repeated dosing

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #653 JH

Posted 04/28/2008