Targeted Engineered Cell Microfactories as a Cancer Therapy

Approaches towards targeting cancer are becoming ever more sophisticated, even as the same basic goal remains unchanged: deliver far lower doses of cell-killing treatments to a far smaller area, even to individual cancer cells where possible, reducing side-effects and damage to everything except the targeted tumor or cancer cells. There are many possible ways to achieve this end, and this one has many potential applications beyond merely cancer treatment:

Attacking the perennial problem of systemic toxicity from typical chemotherapy treatments, researchers have engineered therapeutic cells encapsulated in nanoporous capsules to secrete antitumor molecules from within the tumor. "We have engineered cells that locally convert a nontoxic substance into an antitumor agent. We can encapsulate cells in nanoporous capsules, which ensures the cells are localized and immunoisolated. This immunoisolated micro-factory can remain in the tumor, providing a permanent and renewable source of therapeutic molecules for long-term cancer management."

Engineered bacterial cells that are designed to express therapeutic enzymes under the transcriptional control of remotely inducible promoters can mediate the de novo conversion of nontoxic prodrugs in their cytotoxic forms. In situ cellular expression of enzymes provides increased stability and control of enzyme activity as compared to isolated enzymes. The team engineered Escherichia coli (E. coli), which was designed to express cytosine deaminase at elevated temperatures under the transcriptional control of a thermo-regulatory promoter cassette. This constituted the thermal switch to trigger enzyme synthesis. They subsequently co-encapsulated the cells with magnetic iron oxide in immunoprotective alginate microcapsules and then remotely triggered cytosine deaminase expression by alternating magnetic field-induced hyperthermia.

The goal of localizing therapy to avoid systemic toxicity from chemotherapy is the impetus for the vision to ultimately encapsulate a library of therapeutic cells that will take cues from their microenvironment and secrete appropriate antitumor molecules. Looking forward, the work will focus on using these microencapsulated cells to stimulate the immune system to act against tumors, as well as activating drug synthesis.

Link: http://cancer.dartmouth.edu/about_us/newsdetail/73456/

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