# Translating cellular immunotherapies for autoimmunity to canine clinical trials

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $859,159

## Abstract

Project summary:
Autoimmunity occurs when the body's immune system mistakenly attacks normal tissues, leading to disease.
Treatments for autoimmunity chronically suppress the immune system, which risks fatal infection; thus the
ideal therapy would eliminate only the disease-causing autoimmune cells while preserving normal immunity.
We recently developed a novel gene-engineered chimeric autoantibody receptor T cell (CAAR-T) therapy that
uses the autoantigen targeted in disease to direct T cell cytotoxicity against only those B cells that express
autoantigen-specific B cell receptors (BCRs). We have shown that CAAR-Ts cause complete histologic and
serologic remission of autoantibody (autoAb)-mediated disease in an experimental mouse model and engraft
to form memory CAAR-Ts that can provide lasting protection against disease recurrence. In considering how to
translate CAAR-T technology to first-in-human trials, a challenge arises given that most autoimmune patients
do not face imminent death from their disease, unlike the first cancer patients treated with gene-engineered
cellular therapies. The current preclinical pipeline relies on mice whose disease is artificially induced and
treated shortly after disease induction. Cytokine release syndrome does not occur in mice despite being one of
the most common toxicities in cancer patients. The field has not pursued better preclinical models given the
risks of time and money involved in experimenting in a new animal species. Given the curative potential for
CAAR-T in autoimmunity and the increasing interest in developing cellular therapies for non-oncologic
indications, we believe it is now crucial to establish a higher preclinical standard. We thus seek to establish
dogs with naturally occurring autoimmune disease as an ideal preclinical system for assessing cellular
immunotherapies, which we believe will better predict the safety and efficacy of human therapies than
experimental mouse models. This proposal meets the high-risk, high-reward nature of the transformative R01
program, as gene-engineered cellular therapies have never been tested in any naturally occurring autoimmune
disease. The successful treatment of autoimmunity in dogs with CAAR-T would not only be a breakthrough in
veterinary medicine, but would also establish dogs as an ideal species for preclinical validation of human
cellular immunotherapies and provide compelling evidence for doctors and patients to enroll for future CAAR-T
first-in-human trials. Ultimately, our work could facilitate the translation of cellular immunotherapies for a broad
range of canine and human diseases.

## Key facts

- **NIH application ID:** 9982789
- **Project number:** 5R01AR075337-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** NICOLA J MASON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $859,159
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982789

## Citation

> US National Institutes of Health, RePORTER application 9982789, Translating cellular immunotherapies for autoimmunity to canine clinical trials (5R01AR075337-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982789. Licensed CC0.

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