Researchers from University of Zurich and California Institute of Technology utilize an Adenovirus 5 virion with anti-HER2 TZB antibody (Herceptin) expressing payload to treat orthotopic human HER2 positive tumors in mice. Virion was modified with bispecific multivalent DARPin with external specificity to HER2 receptor, and shielded with scFV directed to coagulation factor X-binding sites on the viral hexon trimer. Biodistribution analysis using PACT 3D imaging showed specific transduction of tumor cells and sustained recombinant antibody production.
“The SHREAD gene therapy platform for paracrinedelivery improves tumor localization and intratumoraleffects of a clinical antibody” Sheena N. Smith, Andreas Plückthun, et al. PNAS (2021) Vol. 118 No. 21 e2017925118