Authors:

Arjun Ratan

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About Paper:

Glioblastoma is an aggressive and treatment-resistant brain cancer with limited therapeutic options. Localized, sustained drug delivery directly into tumors could overcome many limitations of current treatments and conventional therapies, including poor drug penetration and systemic toxicity, and engineered bacteria offer a promising strategy for such an approach. This project applied synthetic biology to engineer E. coli strains capable of delivering therapeutic payloads directly into glioblastoma tumors, thus reducing off-target toxicity. First, the E. coli was engineered to eliminate inflammation and reduce risk, and this strain alone led to prolonged survival in tumor-bearing mice. Several candidate toxins and bioactive molecules were selected for their potential to target diverse tumor cell populations, addressing the highly heterogeneous nature of glioblastoma. Therapeutics were chosen based on either their ability to directly induce tumor cell death or to elicit a robust immune response against tumor cells. Engineered bacterial strains were constructed using molecular cloning techniques, and first tested in glioblastoma cell cultures, where cell viability assays quantified therapeutic efficacy. Strains were subsequently evaluated in vivo through intracranial injection in mouse models bearing grafted glioblastoma tumors. Following administration of bacteria, survival curves, body weight measurements, and bacterial presence within tumors and other vital organs were monitored to assess both efficacy and off-target effects. Together, this work demonstrates the feasibility of using engineered bacteria for precise, localized therapeutic delivery and provides a foundation for the development of clinically translatable bacterial therapies for the treatment of glioblastoma.

Source:

Columbia / Art History, Classics / 2028

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Co-authors:

Arjun Ratan