# Optimization of CAR-Bacteria for Oral Cancer

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $175,429

## Abstract

ABSTRACT
 The goal of this project is to explore the feasibility of generating Chimeric Antigen Receptors (CARs)
expressed by bacteria. Instead of using T cells, we propose to explore the idea and use of bacteria to mediate
the targeted destruction of cancer cells. In addition, we explore the possibility that we could target CAR-bacteria
to specific major histocompatibility complex (MHC)-neopeptide complexes (pMHC) on tumor cells. We call these
engineered bacteria cells CAR-bacteria. Current CAR-expressing T cells provide durable responses but have
three main limitations: specificity, toxicity, and feasibility. This study will address all three concerns. In this
proposal, we target engineered bacterial lysis to head and neck or cervical cancer cells expressing HLA-A2-E7,
a known pMHC on tumor cells infected by human papilloma virus (HPV). The targeting enables anti-tumor protein
production only when a predefined population density of bacteria is reached. This method should dramatically
reduce bacterial colony size and greatly lowers/prevents systemic toxicities. The approach has the potential to
be a therapeutic in HPV-positive oral cancer as it could be administered and controlled as a bacterial mouthwash.
This project combines two innovations leveraging a Synthetically-Evolved Nanobody (SEN) library proven
capable of selectively binding MHC-peptide complexes and combining this specific cancer cell targeting with
synchronized circuit lysis to create CAR-bacteria. Our proposed studies provide proof-of-concept that (1) CARs
can be produced that recognize pMHC, (2) CAR-bacteria localization and colonization can be controlled by tumor
expression of certain pMHC and (3) CAR-bacteria have therapeutic activity against tumor cells that express
specific pMHC. We accomplish these proof-of-concept studies via the following two objectives: (1) Optimize
binding and specificity of CAR-bacteria to HLA-A2-E7 and (2) Check efficacy of CAR-bacteria in an animal model
of head and neck and cervical cancer.

## Key facts

- **NIH application ID:** 10820473
- **Project number:** 5R21CA280794-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jack D Bui
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $175,429
- **Award type:** 5
- **Project period:** 2023-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820473

## Citation

> US National Institutes of Health, RePORTER application 10820473, Optimization of CAR-Bacteria for Oral Cancer (5R21CA280794-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10820473. Licensed CC0.

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