# Gene Expression Analysis of Dog Natural Killer Cells as Immunotherapy Target

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $78,500

## Abstract

Project Summary
Dogs are large, outbred animals that develop cancer spontaneously in the presence of an intact immune system
and in the setting of shared environmental exposures with humans. Humans and dogs also share a paired
evolutionary history which has led to greater similarities between canine and human genomes and microbiomes
than between mouse and human. Together, these traits make dogs an advantageous translational model to
study cancer immunology and cancer immunotherapy. Dog clinical trials allow for the study of complex immune
interactions during therapy while also addressing long-term efficacy and toxicity of cancer immunotherapies.
However, immune dissection requires the development of robust and validated assays and reagents, and high
impact studies using dog immunotherapy are premature until a deeper understanding of dog immunology and
immune biomarkers is realized, especially for natural killer (NK) cells. This proposal will build on our exciting
preliminary data characterizing dog NK cells, including first-in-dog clinical trials of adoptive transfer of dog NK
cells and novel cytokine delivery with inhaled IL-15. In collaboration with the School of Medicine, the School of
Veterinary Medicine, and the Data Intensive Biology Lab which performs cross-species genomic, transcriptomic,
and metagenomic sequence analyses, we will examine dog NK differential gene expression across 1) multiple
stimulatory and steady-state conditions; 2) from dog blood and tumor bio-specimens; and 3) from responding
and non-responding dogs treated with inhaled IL-15 on an investigational dog clinical trial. We will utilize multiple
applications of high-throughput sequencing technologies (RNASeq and single cell RNA sequencing) to establish
more robust and validated gene signatures of resting and activated dog NK cells from both ex vivo and in vivo
conditions with further analysis of dog sarcoma-infiltrating NK cells. We will then compare these gene signatures
to data from high throughput sequencing of murine and human NK cells to bridge species differences and
facilitate clinical translation. Ultimately, knowledge of the role of canine NK cells in immune defense and cancer
therapy is limited, and it remains unclear whether this is due to biological differences across species or limited
reagents for investigation. Results from this proposal will extend the important link that canine studies provide
between murine pre-clinical studies and human clinical trials, for cancer immunotherapy research in general but
especially for NK studies where high impact clinical translation has remained elusive.

## Key facts

- **NIH application ID:** 10372182
- **Project number:** 5R03CA252793-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Robert J. Canter
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,500
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372182

## Citation

> US National Institutes of Health, RePORTER application 10372182, Gene Expression Analysis of Dog Natural Killer Cells as Immunotherapy Target (5R03CA252793-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372182. Licensed CC0.

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