"Paracrine delivery of therapeutic biologics"
Sheena Smith, Department of Biochemistry, University of Zurich
Time and location: June 3rd at 13.30, MV Lecture Hall (Hörsalen). Coffee and cake at 14.30.
Abstract A major limitation of strategies utilizing biologics for the treatment of cancer is achieving high local concentrations within the tumor microenvironment. In situ production of biologics (e.g. antibodies, cytokines) by tumor cells provides an attractive alternative to treatment with repeated high bolus injections, as secretion by the tumor itself could provide high local concentrations where they are needed most while sparing healthy tissues from potential off-target toxicity. To accomplish this goal, we have developed a gene therapy platform in which adenoviral ‘Trojan Horses’ harboring the genes for secreted therapeutic payloads are engineered to transduce tumor or stromal cells specifically. These ‘Trojan Horses’ convert a subpopulation of cells within the tumor microenvironment into therapeutic ‘biofactories’ that secrete biologics in a paracrine fashion. We propose that this delivery approach could reduce the risk of tumor escape and provide a much safer alternative to systemic administration.
Biography Sheena Smith is a postdoctoral fellow at the University of Zürich in the laboratory of Andreas Plückthun. Her research focuses on the development and implementation of protein engineering strategies for the generation and delivery of cancer therapeutics. Sheena received her PhD in 2014 from the University of Illinois at Urbana-Champaign where her research focused on the engineering of T cell receptors as candidates for targeted immunotherapies. Notably, she developed a semi-rational design platform that allows T cell receptors to be engineered entirely in vitro against cancer biomarkers.
 Schmid, M. et al. Adenoviral vector with shield and adapter increases tumor specificity and escapes liver and immune control. Nat Commun 9, 450, doi:10.1038/s41467-017-02707-6 (2018).
 Dreier, B. et al. Development of a generic adenovirus delivery system based on structure-guided design of bispecific trimeric DARPin adapters. Proc Natl Acad Sci U S A 110, E869-877, doi:10.1073/pnas.1213653110 (2013).