- David Lambertson
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.
- Immunotoxins (antibody conjugates) that remain active for longer time in the body can be used for treatment of various types of cancers
- Although the technology can be applied to any cancer, the inventors have demonstrated effectiveness with MM
- The MM market has exceeded US$15B with a compound annual growth rate CAGR of 6.7%
- Addition of albumin binding domains (ABDs) to immunotoxins lowers the required dose, resulting in fewer non-specific side effects
- Addition of ABDs does not interfere with target specificity; instead, indirectly improves therapeutic activity
- Ability to change the targeting domain allows for dynamic approach to specifically treat various cancers
- ABDs introduced into the toxin portion of the RIT dramatically increases their half-life in the circulation and antitumor activity in mice
Ira Pastan MD (NCI), Junxia Wei Ph.D. (NCI), Masanori Onda MD, Ph.D. (NCI), Tapan Bera Ph.D. (NCI), Mitchell Ho Ph.D. (NCI)
- Pre-clinical (in vivo)
Shancer Z, et al. Preclinical development of anti-BCMA immunotoxins targeting multiple myeloma. [PMID 30272049]
- U.S. Provisional: U.S. Provisional Patent Application Number 62/559,926, Filed 18 Sep 2017
- U.S. Patent Filed: U.S. Patent Application Number PCT/US2018/051418 , Filed 18 Sep 2018
- E-263-2011 - Increased Therapeutic Effectiveness of PE-Based Immunotoxins