Immunotoxins with Deletions in Domain II that Remove Immunogenic Epitopes with Minimal Loss of Cytotoxic Activity
Description of Invention:
Anti-CD22 immunotoxins consist of a disulfide-linked FV (VH/VL) antibody fragment recombinantly linked to a toxic moiety capable of killing cells. In particular, a 38-kDa active fragment of Pseudomonas exotoxin A (PE38) containing three specific domains (domain Ib, domain II and domain III) has been used successfully in these immunotoxins. These immunotoxins have been shown to have activity against various forms of cancer, such as hairy cell leukemia and chronic lymphocytic leukemia, and are currently being evaluated in clinical trials.
This technology involves the development of a less immunogenic form of anti-CD22 immunotoxins. Specifically, the inventors have removed all of domain Ib and the majority of domain II from the PE38 portion of the immunotoxin. The resulting construct maintains a similar cytotoxicity to the larger immunotoxin, but with lowered immunogenicity.
Application:
Treatment of cancers associated with the increased expression of CD22, such as leukemia and lymphoma.
Advantages:
Less immunogenic immunotoxin results in improved cytotoxicity
Targeted therapy decreases non-specific killing of non-cancerous cells
Cancer -Therapeutics-Immunoconjugates-Mab Cancer -Therapeutics-Immunoconjugates-Toxins Cancer -Therapeutics
For Additional Information Please Contact: David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220
