# A microbiome-informed platform for the development and testing of bacterial therapies for colorectal cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $568,527

## Abstract

Project Summary
There is a clear imperative to develop potent, cost effective therapeutics to confront the
challenge cancer poses to society. Here we address this need by developing synthetically
engineered cells effective against a broad range of cancer types with a special emphasis on
colorectal cancer (CRC). This cancer type is the second most common cause of cancer death
in the US, with more than 50,000 Americans dying every year. Recent research demonstrates
the power of genetic engineering to make significant advances towards more efficacious cancer
therapy. The introduction of genetically engineered cells, such as chimeric antigen receptor T
(CAR T) cells, has shown great promise for treating many types of B cell malignancies, but
unfortunately targeting CAR T cells to solid tumors remains challenging. In this project we will
use the tools of synthetic biology to make new engineered therapies based on bacterial rather
than mammalian cells. Certain bacterial species have demonstrated a useful ability to “home in”
and selectively colonize solid tumors without infecting healthy tissue. This tumor targeting
property will be exploited in the proposed work to deliver safe, effective therapies directly to the
locations where they are needed most: the solid core of tumors. Previously we developed a
bacterial therapeutic and tested it in an animal model of metastatic disease. In contrast to other
approaches utilizing bacterial cells, this “lysis strain” does not require specialized genetic
modifications for the secretion of encoded cargo, it simply releases it into the environment when
the cells burst. Initially we will genetically modify the lysis strain to produce a wide range of
therapeutics for testing, including toxins (from bacteria, animals and plants), enzymes,
antibiotics, and apoptotic peptides. Next we will analyze the tumor microbiome from human
samples since we hypothesize that the native bacterial population's composition will provide a
unique signature (analogous to a fingerprint) that can be used to divide tumors into distinct
subtypes. We expect to use these fingerprints to identify other species with superior suitability
for therapeutic delivery in treating CRC. Once identified we will develop two in vitro assays for
testing the candidate strains. We will use microfluidic technology to create a high throughput
co-culturing system for bacteria and a cancer cell line. In parallel, we will develop a co-culturing
system for bacteria and organoids that are generated from the same human tumor samples
which had been previously used for strain identification and fingerprinting. Lastly we will test the
most promising therapies in an animal model of colorectal cancer to determine efficacy in a pre-
clinical model.

## Key facts

- **NIH application ID:** 10397153
- **Project number:** 5R01CA241728-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** JEFF M HASTY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $568,527
- **Award type:** 5
- **Project period:** 2020-05-18 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397153

## Citation

> US National Institutes of Health, RePORTER application 10397153, A microbiome-informed platform for the development and testing of bacterial therapies for colorectal cancer (5R01CA241728-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397153. Licensed CC0.

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