# Engineered gamma delta T cells for systemic correction of dystrophic epidermolysis bullosa

> **NIH NIH R41** · KOMMODO THERAPEUTICS LLC · 2024 · $313,370

## Abstract

ABSTRACT
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe autosomal recessive disease caused by
collagen type VIIa (COL7A1) gene mutations. RDEB is characterized by absent/defective COL7A1 (C7) protein
deposition causing severe blistering, mucosal tissue damage, and aggressive squamous cell carcinoma.
Palliative care is non-curative and cellular therapy options include autologous or allogeneic local and/or
systemic infusion of keratinocytes, fibroblasts, mesenchymal stromal cells (MSC), or hematopoietic
stem/progenitor cells (HSPC). None of these currently employed treatment options resolve the full pathological
spectrum of RDEB. Active wound areas persist, and mucosal disease remains highly refractory to intervention
contributing to significant morbidity. Keratinocytes and fibroblasts, the primary C7 producing cells, show limited
migration and persistence following localized injection. MSC and HSPC have broad circulatory potential,
however, they produce comparatively low levels of C7 and residence in the skin or mucosa is not well
established. Thus, it is essential to develop more efficacious cellular therapies capable of accessing skin and
mucocutaneous tissues. γδ T cells are abundant within skin and mucosa, and due to their MHC-unrestricted
nature are compatible with allogeneic transfer, however they do not naturally produce C7. Our approach will
employ a highly efficient and clinical stage non-viral transposon platform to engineer γδ T cells to produce high
levels of endogenous C7. We hypothesize that the tissue migratory properties of γδ T cells—particularly to the
skin and mucosa—as well as their demonstrated allo-compatibility, make them uniquely suited for therapeutic
delivery of C7 protein. In Aim 1 we will define a genome engineering strategy to confer high C7 expression in
human γδ T cells, and test critical safety parameters and commercial feasibility. In Aim 2, we will evaluate the
ability of engineered allogeneic γδ T cells to home to skin and mucosa, deposit C7, and ameliorate pathology
in an immunodeficient mouse model of RDEB, amenable for testing of these engineered human cells. Further,
we will test the effect of zoledronate induced in vivo expansion of the engineered Vγ9Vδ2 T cell subset on
therapeutic efficacy. Our approach is a highly novel and innovative allogeneic strategy designed to address key
limitations of current cellular therapies for RDEB. The application of engineered γδ T cells represents an
attractive protein delivery strategy with high translational potential for RDEB, other inherited mucocutaneous
disorders, and a multitude of diverse disorders treated by cell/stem cell transplant.

## Key facts

- **NIH application ID:** 10919924
- **Project number:** 1R41AR083760-01A1
- **Recipient organization:** KOMMODO THERAPEUTICS LLC
- **Principal Investigator:** Nicole J. Shirkey-Son
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $313,370
- **Award type:** 1
- **Project period:** 2024-08-22 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919924

## Citation

> US National Institutes of Health, RePORTER application 10919924, Engineered gamma delta T cells for systemic correction of dystrophic epidermolysis bullosa (1R41AR083760-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10919924. Licensed CC0.

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