# Engineering tumor-targeting bacteria to sense and deliver therapeutics

> **NIH NIH F99** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $45,520

## Abstract

Project Summary
The ability to engineer living cells as intelligent therapeutic agents is poised to transform current cancer treatment
paradigms. Based on the inherent growth specificity of some natural and exogenous bacteria to solid tumors,
microbes have been explored as programmed vehicles to deliver therapeutics to tumor environments. However,
a universal challenge for developing this next-generation living therapy is the lack of tools to study the dynami-
cally interacting population of bacteria and cancer cells. Consequently, the vast majority of the past studies have
relied on animal models that only test a handful of therapeutic candidates and provide limited spatiotemporal
information. To address this challenge, I have recently developed a 3D multicellular coculture platform that ena-
bles high-throughput characterization of bacteria in tumor spheroids, assessing dynamics of multicellular inter-
actions and predicting therapeutic efficacy in vivo.
 In this proposal, I will leverage the 3D coculture technologies and synthetic biology tools to construct novel
bacterial systems that sense and express therapeutics specifically in tumors. In the F99 phase, I will engineer
tumor-homing bacteria to dynamically regulate production of cytotoxic molecules in response to tumor shrinkage.
Specifically, as the cancer cell death increases the level of oxygen in the tumor core, I will engineer a bacterial
biosensor circuit to monitor this change in the tumor microenvironment. By detecting rises in oxygen levels,
which indicate extensive therapeutic progression, this gene circuit will reduce the therapeutic level produced,
minimizing off-target toxicity. In the K00 phase, I will repurpose tumor-homing bacteria to target and eradicate
oncogenic F. nucleatum in colorectal cancer. I will apply the 3D coculture platform to screen anti-F. nucleatum
peptides delivered by bacteria to tumor spheroids. Orthotropic mouse cancer models will be used to assess the
F. nucleatum elimination, effect on commensal microbiota, and cancer progression. Collectively, the proposed
work will utilize a novel engineering framework to develop effective bacterial cancer therapies towards clinical
translation.

## Key facts

- **NIH application ID:** 10065290
- **Project number:** 1F99CA253756-01
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Tetsuhiro Harimoto
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065290

## Citation

> US National Institutes of Health, RePORTER application 10065290, Engineering tumor-targeting bacteria to sense and deliver therapeutics (1F99CA253756-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065290. Licensed CC0.

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