# Gene Expression Analysis of Dog Natural Killer Cells Following Immunotherapy with Molecularly Targeted Radionuclide therapy or Inhaled IL-15

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $250,094

## Abstract

Project Summary
Companion dogs are large, outbred animals that develop cancer spontaneously in the presence
of an intact immune system, a native autochthonous tumor microenvironment, and in the setting
of shared environmental exposures with humans. In fact, humans and dogs 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, and
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 a deeper
understanding of dog immunology and immune biomarkers is necessary to achieve high impact
translational studies, especially in the context of natural killer (NK) cells where significant
species differences are known to exist. This proposal will build on exciting data from the
collaborating institutions with significant expertise in comparative oncology and novel
immunotherapy trials underway. Using pre- and on-treatment PBMC samples from dogs on trial
receiving novel and “first-in-class” immunotherapies which stimulate NK cells, we will use RNA
sequencing to examine NK differential gene expression to 1) establish robust and validated
gene signatures of resting and activated dog NK cells from both clinical trial cohorts; 2) analyze
NK gene signatures from responding and non-responding patients; and 3) evaluate for
similarities and differences in NK gene signatures between respective NK stimulatory
immunotherapies which are anticipated to have overlapping, but distinct, mechanisms of action.
Results from this proposal will extend the important link that canine studies provide between
murine pre-clinical studies and human clinical trials and facilitate the rapid translation of novel,
potentially high impact NK therapies to both dog and human patients with aggressive cancers.

## Key facts

- **NIH application ID:** 10287107
- **Project number:** 3U01CA224166-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Robert J. Canter
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $250,094
- **Award type:** 3
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287107

## Citation

> US National Institutes of Health, RePORTER application 10287107, Gene Expression Analysis of Dog Natural Killer Cells Following Immunotherapy with Molecularly Targeted Radionuclide therapy or Inhaled IL-15 (3U01CA224166-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10287107. Licensed CC0.

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