# Designer EcN for treatment of solid tumors

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $249,442

## Abstract

Current modalities for the treatment of solid tumors include surgical resection, chemotherapy, and radiation,
approaches that often are not sufficient to lead to cure and are generally associated with numerous side effects.
Immunotherapy based interventions, including immunostimulatory monoclonal antibodies that block immune
checkpoints, are revolutionizing the treatment of cancers as they provide a means to engage the patient’s own
immune system to recognize and fight cancer. However, the systemic administration of these therapies is often
associated with marked adverse reactions that can be very serious, particularly when multiple agents are used
in combination. Novel means to target the efficient delivery of immunostimulatory molecules directly to tumors
and neoplasmic deposits are needed. Interestingly, multiple bacterial species selectively colonize and proliferate
to high titers in tumors where some like Salmonella and Clostridial species promote tumor regression and even
clearance, at least in part by inducing host inflammatory responses. Attenuated versions of these bacteria are
observed to effectively eradicate tumors in mouse models, but have shown limited success in human trials, likely
because they are rapidly cleared from the systemic circulation such that the bacteria never reach and establish
residence in the tumors. Interestingly, Nissle 1917 E. coli (EcN), a probiotic strain commonly used in the
treatment of inflammatory bowel disease, also homes to and colonizes solid tumors. Yet, despite reaching titers
as high as 1010 colony forming units of bacteria/gram of tumor, EcN induces no response. Here we propose to
test variants of EcN capable of delivering immunostimulatory nanobodies that block that activity of immune
checkpoint proteins directly into the microenvironment of solid tumors. We will then investigate the ability of these
strains to promote tumor regression using a mouse model of melanoma. We will also conduct genome-wide
transposon insertion screens to identify EcN determinants involved in the homing to and proliferation within solid
tumors. It is our expectation that at the completion of this exploratory 2-year grant we will have proof-of-concept
that the programmable immune-based bacteriotherapy we are developing has the potential to become a novel
cancer therapeutics platform.

## Key facts

- **NIH application ID:** 10459848
- **Project number:** 1R21CA249995-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** CAMMIE LESSER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,442
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459848

## Citation

> US National Institutes of Health, RePORTER application 10459848, Designer EcN for treatment of solid tumors (1R21CA249995-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10459848. Licensed CC0.

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