# Genetically engineered macrophages to treat pulmonary infections

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $276,097

## Abstract

PROJECT SUMMARY
Bacterial pneumonia is a leading cause of morbidity and mortality worldwide. Increasing antimicrobial
resistance among common agents of bacterial pneumonia necessitates the development of new therapeutic
strategies. In this project, we focus on two resistant pathogens that are public health threats. Burkholderia
pseudomallei (BP) is a common etiology of pneumonia (pneumonic melioidosis) in Southeast Asia and
northern Australia. Pneumonic melioidosis is lethal in 22-50% of cases despite treatment. BP is a facultative
intracellular pathogen that is inherently resistant to many antibiotics and requires prolonged courses of therapy.
Klebsiella pneumoniae (KP) is an extracellular pathogen that is a well known cause of community- and
healthcare-associated pneumonia. KP has become increasingly resistant to carbapenems and third generation
cephalosporins. Infections caused by resistant strains of KP are difficult to treat, prolong hospital stays, and are
associated with high mortality. BP and KP are representative of the urgent need to develop new therapies to
treat resistant lung infections. This project brings together three investigators from distinct disciplines to tackle
this challenge. Drs. West and Skerrett are established researchers in pulmonary host defense against bacterial
lung infections. They have created murine models of bacterial respiratory infection including BP (and surrogate
organism, B. thailandensis) infection and KP. These bacterial respiratory infection models have been used to
investigate host and bacterial factors and to evaluate therapeutics. Dr. Crane, a cancer immunotherapy
researcher, has developed a novel and flexible system to create genetically engineered macrophages (GEMs)
to produce a range of secreted proteins over a month in vitro or in vivo. Administered intravenously to mice,
GEMs accumulate at high levels in the lungs for at least 4 days. Others have reported that airway delivery of
macrophages results in durable localization of these cells within the lungs for months. Thus, intravenous or
pulmonary delivery of GEMs may be a novel, versatile therapeutic strategy against lung infections. The central
hypothesis of this proposal is that GEMs that produce pro-inflammatory and/or antimicrobial peptides and
home to the site of infection can augment host resistance to respiratory infections caused by pathogens such
as BP and KP. This hypothesis will be tested as follows: Aim 1. Develop and test GEMs with enhanced
bacterial killing functions that produce the cytokine interleukin 12 (IL-12) or antimicrobial peptide CRAMP (the
mouse homolog of human cathelicidin). Aim 2. Define localization and the inflammatory responses induced by
IL-12- or CRAMP-expressing GEMs adoptively transferred in vivo. Aim 3. Determine whether the adoptive
transfer of IL-12- or CRAMP-expressing GEMs augments resistance to acute bacterial pneumonia caused by
B. thailandensis or K. pneumoniae. This innovative project tests two novel an...

## Key facts

- **NIH application ID:** 9977009
- **Project number:** 1R21AI149400-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Courtney Crane
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $276,097
- **Award type:** 1
- **Project period:** 2020-02-06 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977009

## Citation

> US National Institutes of Health, RePORTER application 9977009, Genetically engineered macrophages to treat pulmonary infections (1R21AI149400-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977009. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*