Available Technology

A Fold-Back Diabody Format for Diphtheria Toxin-Based Immunotoxins That Can Increase Binding and Potency

NIH inventors, in collaboration with Scott and White Memorial Hospital inventors, have developed new immunotoxins comprising a mutant diphtheria toxin linked to an anti-prostate specific membrane antigen (PSMA) fold-back diabody. The fold-back diabody construct has a shortened linker region between the heavy and light chains of the antibody variable domain. This construct allows interactions between the longer-linked variable domains while preventing interactions between the shorter-linked variable domains. This results in increased efficiency of epitope recognition and delivery to the appropriate target cells. These immunotoxins can be used for the treatment of cancers that overexpress PMSA, with specific application against prostate cancer.
Abstract: 
NIH inventors, in collaboration with Scott and White Memorial Hospital inventors, have developed new immunotoxins comprising a mutant diphtheria toxin linked to an anti-prostate specific membrane antigen (PSMA) fold-back diabody. The fold-back diabody construct has a shortened linker region between the heavy and light chains of the antibody variable domain. This construct allows interactions between the longer-linked variable domains while preventing interactions between the shorter-linked variable domains. This results in increased efficiency of epitope recognition and delivery to the appropriate target cells. These immunotoxins can be used for the treatment of cancers that overexpress PMSA, with specific application against prostate cancer.
Benefits: 
Increased potency of 10-40-fold resulting from the use of the fold-back diabody construct. - First treatment with applications to metastatic prostate cancer. - Pichia pastoris production process of the fold-back immunotoxin can be used to scale up for GMP production.
applications: 
Inventors: 

David Neville Jr (NIMH)

Patent Number: 
PCT/US2008/009321 US Application No. 60/953,416 US Application No. 12/671,629
Internal Laboratory Ref #: 
E-268-2007/0 Updated: Nov 9, 2015
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