# Engineered bacterial in situ vaccines against oral cancer.

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $434,170

## Abstract

PROJECT SUMMARY.
Immunotherapy has become an emerging standard-of-care (SOC) for many different cancer types. However,
only 15-20% of patients receive durable benefit. Other limitations include the toxicity of systemically-delivered
immunomodulators which may require frequent, high doses and lead to immune-related adverse events (irAEs).
The risk of severe, and potentially fatal, irAEs increases as the field moves towards immune/immune and
immune/SOC combination therapies. As the “front line” of tumor/immune interaction, the tumor immune
microenvironment (TIME) is a critical locus of immunomodulation, where the kinds of immunocytes in the TIME
predict the likelihood of response to diverse immunotherapies. One strategy to favorably modulate the TIME
following standard-of-care surgical resection, is to localize and sustain immunotherapy at the resection site and
tumor-draining lymph nodes, reversing the immunosuppressive post-surgical wound healing immune
microenvironment while promoting anti-tumor effector cell immunity. This in situ therapeutic cancer vaccination
approach can enhance local concentration of potent therapies while minimizing systemic exposure and likelihood
and severity of irAEs. The use of synthetically engineered microbes as platforms for cancer immunotherapy
provides the potential to intelligently direct and modulate immune cells in situ. Our biomaterial-encapsulated
engineered bacteria are at the forefront of this field, with the ability to carry out targeted localization of engineered
non-pathogenic E. coli releasing TIME-modulating therapeutic molecules. This allows for reduced off-target
toxicity, dose-sparing, and targeting of multiple immune pathways to address the heterogeneous nature of
cancers. The overall hypothesis of this proposal is that our living in situ vaccination platform EcN-IL12Vax can
achieve localized and controlled delivery of immunostimulatory cytokines, targeting the post-tumor resection
immune microenvironment and tumor-draining lymph nodes (TDLNs) to produce robust anti-tumor responses
that eliminate both local tumor recurrence and lymph node metastases. Importantly, we hypothesize that our use
of bacteria will stimulate the innate immune system while their IL-12 secretion will stimulate the adaptive immune
system, thereby leading to enhanced residual tumor killing. We will characterize the immune response and
efficacy of EcN-IL12Vax in two Specific Aims: Aim 1 will develop potent and programmable non-pathogenic E.
coli as part of a biomaterial-encapsulated engineered bacterial in situ vaccination platform capable of secreting
the immunostimulatory cytokine IL-12. Aim 2 will examine how the duration of IL-12 secretion from EcN-IL12Vax
affects both the efficacy and durability of the immunologic response within the immunosuppressive tumor
resection cavity immune microenvironment and tumor-draining lymph nodes. This transformative approach will
provide the field with an invaluable in situ cancer vaccine p...

## Key facts

- **NIH application ID:** 11035580
- **Project number:** 1R21DE034543-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Jeffrey Jay Tabor
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $434,170
- **Award type:** 1
- **Project period:** 2024-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035580

## Citation

> US National Institutes of Health, RePORTER application 11035580, Engineered bacterial in situ vaccines against oral cancer. (1R21DE034543-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11035580. Licensed CC0.

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