Cancer Immunotherapy using a DNA Vaccine Encoding the Translocation Domain of a Bacterial Toxin Linked to a Tumor Antigen

DNA vaccines are an attractive approach for tumor immunotherapy. One concern about DNA vaccines is their potency since they do not amplify themselves. Domain II of Pseudomanas Exotoxin A (ETA(dII))has been shown to translocate from extracellular and vesicular compartments into the cytoplasm, which presents an opportunity to enhance MHC I presentation to CD8+ T cells. Johns Hopkins University researchers have created chimeric genes between ETAd(II) and HPV-16 E7 and vaccinated C57BL/6 mice with the following constructs 1) ETAd(II), 2) HPV-16 E7, 3) ETAd(II) fused with E7, 4) ETAd(II) and E7 or 5) an empty vector. Vaccination with the fusion protein increased E7-specific CD8+ T cells 30-fold. One hundred percent of mice vaccinated with the fusion protein remained tumor free 60 days after tumor challenge. In contrast, only 40% and none of the mice vaccinated with E7 DNA remained tumor free 60 days after tumor challenge in the tumor protective and treatment experiment, respectively. Patent (Set) WO 03/085085

Inventor(s): Wu, T.C.

Type of Offer: Licensing



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