Increased Therapeutic Effectiveness of PE-Based Immunotoxins

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