# Cellular Immunotherapy for Systemic Sclerosis

> **NIH NIH R44** · CELDARA MEDICAL, LLC · 2020 · $730,718

## Abstract

Project Summary
Systemic sclerosis (SSc) is a systemic autoimmune disease that results in widespread fibrosis of the skin and
internal organs, vascular dropout and autoantibody formation. SSc has the highest case fatality rate of any
systemic autoimmune disease and there remain no FDA-approved therapies. Our data and that of others indicate
that the innate immune system is the major driver of fibrosis in SSc. Analysis of gene expression data on samples
collected from SSc patients strongly indicates that alternatively activated macrophages are key drivers of SSc
pathogenesis. The scientific premise of our approach is that the innate immune system, primarily alternatively
activated macrophages (MØs), is a key driver of SSc across multiple end-target organs and the elimination of
such MØs will result in decreased fibrosis. To address this, we designed a novel therapeutic approach to
eliminate alternatively activated MØs. In Phase I studies, we demonstrated that targeted elimination of a
subpopulation of MØs using chimeric antigen receptor (CAR) T cells led to a reduction in skin thickness in a
bleomycin mouse model of skin fibrosis. Moreover, removal of these cells during the development of fibrosis
resulted in an overall reduction of gene expression associated with progression of the disease. Our goal in
Phase II is to further develop a cellular therapy that targets alternatively activated macrophages through the use
of chimeric antigen receptor (CAR) T cells and our lead targeting construct developed in Phase I. We
demonstrated that CAR T cells ameliorated the fibrotic process locally, and anticipate the same impact
systemically. By the end of Phase II, we will have performed the required IND-enabling studies to move this
therapeutic approach into the clinic. The specific aims of this Phase II grant application are: 1) Demonstrate the
therapeutic efficacy of CAR T cells in SSc models; 2) Create human CAR T cells against SSc MØs and optimize
manufacturing production; and 3) Determine anti-CD206 CAR T cell persistence in vivo using a systemic model
of fibrosis.

## Key facts

- **NIH application ID:** 9999399
- **Project number:** 5R44AR073067-03
- **Recipient organization:** CELDARA MEDICAL, LLC
- **Principal Investigator:** Joana M Murad
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $730,718
- **Award type:** 5
- **Project period:** 2017-09-07 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999399

## Citation

> US National Institutes of Health, RePORTER application 9999399, Cellular Immunotherapy for Systemic Sclerosis (5R44AR073067-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999399. Licensed CC0.

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