Technology ID

Increased Therapeutic Effectiveness of PE-Based Immunotoxins

Lead Inventor
Pastan, Ira (NCI)
Onda, Masanori (NCI)
Liu, Wenhai
Therapeutic Areas
Development Stages
Lead IC

Patients receiving immunotoxin cancer therapy 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 epitopes contained within Pseudomonas exotoxin A (PE). 

To improve the therapeutic effectiveness of PE-based immunotoxins through multiple rounds of drug administration, NIH inventors have sought to identify and remove the human B cell epitopes within PE. Previous work demonstrated that the removal of the murine B cell and T cell epitopes from PE reduced the immunogenicity of PE and resulted in immunotoxins with improved therapeutic activity.

This technology involves the identification and removal of major human B cell epitopes on PE by mutation or deletion. Considering these immunotoxins will be administered to humans, the removal of human immunogenic epitopes is important.  The resulting PE-based immunotoxins have increased resistance to the formation of neutralizing antibodies, and are expected to have improved therapeutic efficacy.

Competitive Advantages:

  • PE variants now include the removal of human B-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 in humans
  • Targeted therapy decreases non-specific killing of healthy, essential cells, resulting in fewer non-specific side-effects and healthier patients

Commercial Applications:

  • Treatment of diseases associated with increased or  preferential expression of a specific cell surface receptor such as  hematological cancers, lung cancer, ovarian cancer, breast cancer, and head and neck cancers
Licensing Contact:
Lambertson, David