# Development of a novel lymphocyte engineering approach for treatment of vitiligo

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2022 · $216,480

## Abstract

Project Summary:
 Vitiligo is a common skin depigmentation disorder with an estimated prevalence of 1~4% of the population
worldwide. Vitiligo is phenotypically characterized by non-scaly, white macules with distinct sharp margins
distributed unilaterally on the patients’ skin, caused by systematic destruction of skin melanocytes. It has a
significant impact on the patients’ life both biologically and psychologically. Although multiple mechanisms may
jointly contribute to the development of vitiligo, there is a growing consensus that autoimmune response plays a
key role in this process. Mounting evidence suggest that self-reactive CD8+ T cells are both necessary and
sufficient for destruction of functional melanocytes in vitiligo lesions.
 The treatment of vitiligo remains one of the most difficult challenges for dermatologists. Approximately
40% of patients have relapse of the disease within the first year after the treatment. Cell and gene therapy
provide a promising therapeutic approach for a variety of otherwise terminal or disabling diseases. Adoptive
transfer of engineered lymphocytes, such as chimeric antigen receptor (CAR) T cells has shown tremendous
success in treatment of hematologic malignancies. CAR T cells have been engineered to target activated
myofibroblasts for cardiac fibrosis and autoantibody-producing B cells for potential treatment of pemphigus
vulgaris. However, treatment with CAR T is associated with severe and sometimes lethal increases in systemic
cytokine toxicity. In this regard, natural killer (NK) cells are powerful innate immune effectors cells. NK cells do
not attack healthy self-tissues, nor do they induce the inflammatory cytokine storm as T cells, enabling their
potential application as a safer adoptive cell therapy for many human diseases beyond cancer. The objective of
this exploratory proposal will be to examine the intriguing possibility of CAR NK cell engineering for treatment of
vitiligo. Specifically, we plan to test a β2-microglobulin-based CAR design in conjunction with exogenous
expression of different melanocyte antigens in engineered NK cells. We posit that overexpression of the self-
antigen with a fusion of degron signal domain can lead to efficient antigen presentation through the engineered
MHC I complex containing CAR- β2-microglobulin, which can lead to recognition and destruction of self-reactive
CD8+ T cells. Our study will define a novel paradigm for vitiligo treatment and lay the essential groundwork for
treatment of other autoimmune disease involving self-reactive T cells with CAR-NK platform.

## Key facts

- **NIH application ID:** 10422486
- **Project number:** 1R21AR080761-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Xiaoyang Wu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $216,480
- **Award type:** 1
- **Project period:** 2022-06-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422486

## Citation

> US National Institutes of Health, RePORTER application 10422486, Development of a novel lymphocyte engineering approach for treatment of vitiligo (1R21AR080761-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10422486. Licensed CC0.

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