# MRI-Guided Cryoablation and Imaging-Guided Intratumoral Delivery of STING Agonist Immunotherapy to Target Localized and Metastatic Canine Osteosarcoma

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $615,301

## Abstract

Osteosarcoma (OSA) occurs in both children/young adults and in dogs, with an annual incidence of 450
and 25,000 cases, respectively, making dogs a useful comparative oncology model for the development
of OSA treatments. Unfortunately, outcomes for patients with OSA have plateaued over the past three
decades. Thus, new treatment approaches beyond the standard of care (SOC) surgery and
chemotherapy are sorely needed. As a novel therapy for OSA, our group is developing Magnetic
Resonance Imaging (MRI)-guided cryotherapy in conjunction with image-guided intratumoral injection
of an immune adjuvant. To this end, we will perform a canine clinical trial comparing MRI-guided
cryotherapy alone or in conjunction with intratumoral immune adjuvant administration in spontaneously
occurring, non-metastatic, canine appendicular OSA. The proposed immune correlative studies will
provide crucial insights into the mechanisms of immune regulation in OSA tumors and the immunologic
impact of the therapies to guide future improvements. While cryotherapy directly kills OSA tumor cells,
our intent is to activate the patient’s adaptive immune system against tumor antigens that are presented
from the dying tumor cells, with the addition of intratumoral delivery of an immune adjuvant. Following
local control surgery, we hypothesize that the primed adaptive immune response can delay or prevent
the occurrence of metastatic disease, which is uniformly fatal. Using MRI, one can precisely determine
the extent of tumor tissue that is frozen and killed by cryotherapy without exposure to ionizing radiation.
Others have demonstrated an influx of macrophage and myeloid cells following cryoablation. Via
intratumoral injection, we will deliver a novel Stimulator of Interferon Gene (STING) agonist following
cryotherapy to activate the infiltrating innate immune cells. STING pathway activation results in
extensive cytokine induction, the activation of antigen presenting cells, and subsequent priming of T
cells. Our specific aims are: 1. To determine whether MRI-guided cryoablation of OSA generates an
immune response based on cytokine assays, immunohistochemistry (IHC), and immunoassays that can
prevent metastatic progression, as assessed by non-invasive imaging and thereby increase overall
survival compared to SOC treatment. 2. To characterize the immune response and safety of CT-guided
STING agonist intratumoral administration in canine OSA. 3. To determine whether MRI-guided
cryoablation combined with CT-guided intratumoral STING agonist administration prevents metastatic
disease progression and prolongs survival compared with SOC treatment for OSA. The high incidence
of OSA in dogs with a high rate of metastatic disease provides an ideal animal model with which to study
this novel image-guided treatment of OSA using clinically relevant imaging systems with the potential
for rapid translation and application in other solid tumors.

## Key facts

- **NIH application ID:** 10375449
- **Project number:** 5R01CA239124-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DARA L KRAITCHMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $615,301
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375449

## Citation

> US National Institutes of Health, RePORTER application 10375449, MRI-Guided Cryoablation and Imaging-Guided Intratumoral Delivery of STING Agonist Immunotherapy to Target Localized and Metastatic Canine Osteosarcoma (5R01CA239124-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10375449. Licensed CC0.

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