Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies

Checkpoint inhibitors have revolutionized cancer therapy but only work in a subset of patients and can lead to a multitude of toxicities, suggesting the need for more targeted delivery systems. Because of their preferential colonization of tumors, microbes are a natural platform for the local delivery of cancer therapeutics. Here, we engineer a probiotic bacteria system for the controlled production and intratumoral release of nanobodies targeting programmed cell death-ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) using a stabilized lysing release mechanism. We used computational modeling coupled with experimental validation of lysis circuit dynamics to determine the optimal genetic…

• NS
  National Science Foundation

  Award: 1644869
• UD
  U.S. Department of Defense

  Awards: BC160541, LC160314
• BC
  Breast Cancer Research Foundation

  Award: PC 516160
• NO
  NIH Office of the Director

  Award: R00CA197649-02