Engineered Bacteria Enhance Immunotherapy and Targeted Therapy through Stromal Remodeling of Tumors.

ABSTRACT: Desmoplastic solid tumors are characterized by the rapid build-up of extracellular matrix (ECM) macromolecules, such as hyaluronic acid (HA). The resulting physiological barrier prevents the infiltration of immune cells and also impedes the delivery of anticancer agents. The development of a hypervesiculating Escherichia coli Nissle (ΔECHy) based tumor targeting bacterial system capable of distributing a fusion peptide, cytolysin A (ClyA)-hyaluronidase (Hy) via outer membrane vesicles (OMVs) is reported. The capability of targeting hypoxic tumors, manufacturing recombinant proteins in situ and the added advantage of an on-site OMV based distribution system makes the engineered bacterial vector a unique candidate for peptide delivery. The HA degrading potential of Hy for stromal modulation

SUBMITTER: Thomas SC 

PROVIDER: S-EPMC8770579 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature