# Cell Based Immunomodulation to Suppress Lung Inflammation and Promote Repair

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $704,795

## Abstract

Acute respiratory distress syndrome (ARDS) affects over 300,000 Americans annually with a 43% mortality rate.
Inflammation plays a key pathogenic role in mortality, particularly in the one-third of patients with
hyperinflammatory ARDS. Inflammation also drives subsequent development of pulmonary fibrosis and
interstitial lung disease (ILD) that leads to progressive respiratory failure among ARDS survivors. Cytokines,
such as Interleukin-1 receptor antagonist (IL-1Ra) and Interleukin-10 (IL-10), suppress inflammation and
promote lung repair in ARDS animal models. However, current systemic administration approaches to deliver
these cytokines in therapy remain plagued by poor biodistribution, toxicity, infections due to deleterious systemic
immunosuppression, and paradoxical pro-inflammatory responses, all of which limit clinical translation. We have
overcome these critical limitations by developing an innovative and translational cell therapy platform that
enables sustained locally administration to the lungs. We have engineered retinal pigment epithelial (RPE) cells
to produce IL-1Ra and IL-10 in a more physiologically relevant paracrine fashion at high local concentrations
without systemic absorption and have encapsulated them in alginate-based core-shell capsules, shielding them
from the host immune system and allowing them to serve as a regulatable in situ cytokine “factories”. We have
demonstrated that local delivery modulates inflammation and improves outcomes in ARDS. In this proposal, we
hypothesize that pulmonary implantation of RPE cytokine factories will enable sustained local, and titratable
delivery of IL-1Ra and IL-10 to the lungs, with temporal control. We will develop 2 novel RPE capsule systems
that will be tailored specifically for: (i) airway-instillation (Ai-RPE) that allows direct contact with inflamed alveolar
epithelial surfaces for acute suppression of inflammation and (ii) pleural-instillation (Pi-RPE) which can support
long term RPE cell survival for chronic sustained therapy required to stimulate tissue remodeling. In Aim 1, we
will engineer Ai-RPE IL-1Ra capsules to suppress acute lung inflammation and prevent lung scaring in endotoxin
and viral (influenza) inflammation ARDS rat models. We will incorporate programmable biodegradation for
therapy cessation and airway clearance. In Aim 2, we will validate Pi-RPE for sustained delivery of IL-10 and IL-
1Ra cytokine factories as mono- or combination therapies to reverse pulmonary fibrosis in a bleomycin ARDS
rat model. We will assess the long-term fate of RPE cells in vivo and integrate an apoptotic cell safety switch to
cease therapy post-administration. In Aim 3, the ability to titrate and cease therapy post-implantation in a clinically
relevant fashion will be evaluated in a porcine model. Efficacy of RPE therapy will be tested in a porcine ARDS
model. Overall, these studies will develop therapeutic “off-the-shelf” RPE cytokine factories with sustained
survival and functi...

## Key facts

- **NIH application ID:** 10940864
- **Project number:** 1R01HL174616-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** RAVI K GHANTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $704,795
- **Award type:** 1
- **Project period:** 2024-08-16 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10940864

## Citation

> US National Institutes of Health, RePORTER application 10940864, Cell Based Immunomodulation to Suppress Lung Inflammation and Promote Repair (1R01HL174616-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10940864. Licensed CC0.

---

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