Improving Efficacy of Salmonella-Based Cancer Therapies Through Deletion of Effector Proteins

Presenter: Surya Arunkumar

Faculty Sponsor: Neil Forbes

School: UMass Amherst

Research Area: Biochemistry and Molecular Biology

Session: Poster Session 3, 1:15 PM - 2:00 PM, 165, D4

ABSTRACT

Engineered Salmonella has been developed to increase tumor suppression due to the bacteria’s innate ability to invade tumor cells and deliver therapeutic payloads directly. This bacterial therapy allows for the specific delivery of immune-activating treatments and localized drug delivery. However, injected Salmonella is able to maintain its virulence mechanisms, increasing intracellular survival through immune suppression and decreasing the effectiveness of the cancer immunotherapy since bacterial clearence is essential. This project assesses whether Salmonella-based cancer therapy can be enhanced by deleting Salmonella effector proteins: SpiC and SteE. Effector proteins play a role in increasing Salmonella intracellular survival through various mechanisms. SpiC has been shown to be required for secretion of other SPI II effector proteins due to its role in translocon assembly and has been proven to increase transcription of IL-10, which is known to limit host immune response. SteE has also been shown to increase levels of IL-10. Knockout strains that lacked each of these effector proteins were engineered using recombination and CRISPR gene editing. Levels of IL-10 were assessed with ELISA and levels of other proteins involved in the pathway were assessed with western blotting. We hypothesize that deletion of SpiC will reduce SteE translocation, which in turn will limit IL-10 transcription and STAT3 activation, helping explain SpiC’s role in IL-10 expression. Pro- inflammatory cytokines such as TNF-α will increase. This will promote a stronger immune response compared to wild-type strains because redirecting Salmonella from immune evasion will enhance the safety and efficacy of bacterial cancer immunotherapy.

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