Engineering Prodrug Therapies For Infectious Disease and Cancer Therapy

26 September 2022 09:45 - 10:15

  • Therapeutic platform targets antibiotic and antiviral drugs to cellular compartments such as the lung macrophage to extend PK profiles and potentiate drug activity against bacterial and viral pulmonary pathogens
  • Platform can be engineered to extend the PK profile of small molecule drug regulators of mRNA gene circuits or cell therapeutic regulatory circuits
  • Liver-targeting of drugs has also been shown to hepatocytes to increase therapeutic index via IV or subcutaneous routes of administration
  • Tumor-associated macrophages and antigen-presenting cells can be targeted with adjuvanting immune-modulators for use in immune-therapies and vaccines
A polymeric prodrug platform has been developed for infectious disease and cancer therapeutics.  The “drugamers” can be designed to target the macrophage reservoir in organs and tumors, and with controlled and extended pharmaco-kinetic profiles. The polymeric prodrugs have been initially developed against pulmonary infections, where they have shown excellent activity against highly lethal bacterial disease models. The platform has been further broadened to include other pulmonary infectious disease therapy including antiviral therapeutics against Covid. The macrophage- and APC-targeting properties also have opened new applications for immune-therapy of cancer and vaccines, in concert with cell and biologic drug combination therapy. In addition, this platform has been extended to target drugs to the liver, using GalNAc targeting of liver hepatocytes to improve PK/PD and therapeutic index.   Finally, the polymeric prodrugs are also showing promise as a new long-acting depot product for antiviral therapies, including HIV prophylaxis. Recent advances across these applications will be covered.

Professor Patrick Stayton, Distinguished Career Professor, Director, Molecular Engineering & Sciences Institute, University of Washington