New Class of Immunotoxins with Extended Half-Life and High Anti-Tumor Activity

Recombinant immunotoxins (RITs) constitute a promising solution to hematologic cancers (e.g., Multiple Myeloma [MM]). RITs are chimeric proteins composed of a targeting domain fused to a bacterial toxin. Upon binding to a cancer cell displaying the target antigen, RITs are internalized, metabolized and the released toxin kills the cell. While highly active and effective, current RITs have short half-lives, requiring them to be used in high concentrations for treatment. At such high concentrations, RITs may show nonspecific activity and kill healthy cells.

Scientists from the National Cancer Institute’s (NCI) Laboratory of Molecular Biology developed a new class of RITs active in low doses and demonstrating prolonged stability in the body. Specifically, albumin binding domains (ABDs) have been introduced into the toxin portion of the RIT. ABDs allow the RIT to bind to serum albumin – extending the life of the RITs while not interfering with target specificity or cytotoxicity. The inventors have shown that low doses of the novel RITs display highly specific cytotoxicity in mouse models of MM. This approach can also be applied to other cancers by changing the targeting domain on the RIT.

NCI is seeking parties interested in licensing this invention and/or collaborating to further develop and commercialize the new class of RITs with longer half-lives for treatment of cancers, including MM.