# Intratumoral Cytokine Immunotherapy Studies in Companion Canine Cancer Models

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $521,821

## Abstract

Project Summary
This is a new MPI R01 proposal bringing together protein engineering for immunotherapy
(Wittrup, MIT) with comparative oncology/veterinary medicine (Fan, UIUC) to test clinical
strategies for combining radiotherapy with intratumoral cytokine administration/retention in pet
dogs with melanoma, at the UIUC veterinary clinic. We have developed a strategy for retaining
injected cytokines (IL-2 and IL-12 in particular) in situ by expressing them as fusions to natural
collagen-binding domains. This approach has been found to be safely curative in challenging
murine transplant and GEM tumor models, and will now be advanced into a more faithful model
for human cancer: spontaneous canine melanoma. These tumors arise spontaneously in
outbred populations, and undergo a natural progression of immunoediting prior to clinical
presentation. Canine melanoma exhibits pathophysiology similar to human melanoma, including
the presence of immune infiltrated, excluded, and desert subtypes. In Aim 1, we will exploit the
more-realistic anatomy of these tumors to optimize the micropharmacokinetics of intratumoral
administration, establishing foundational principles with respect to injectable volume fractions,
needle types, and numbers of sites. In Aim 2, we will test the therapeutic hypothesis that
precisely temporally programmed intense localized cytokine stimulation can be optimally
combined with radiation therapy so as to prime a strong T cell vaccinal response with
consequent systemic impact on efficacy. In Aim 3, we will perform a clinical trial in canine
melanoma to rigorously compare alternative dose scheduling for intratumoral cytokine therapy
following irradiation. We hypothesize that the time delay prior to cytokine injection will have a
critical, all-or-nothing effect on outcomes. This intradisciplinary collaboration has commenced,
and exciting preliminary treatment data is presented herein.
The overarching objective of this project is to develop improved human cancer immunotherapy
protocols that combine intratumoral immunotherapy with local radiation. Multiple previous
clinical trials in this area have yet to realize the full promise of this approach, but by performing
rapid design-build-test-learn cycles in spontaneous canine melanoma, we hope to converge
more efficiently to efficacious strategies.

## Key facts

- **NIH application ID:** 10445377
- **Project number:** 1R01CA271243-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** TIMOTHY M FAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $521,821
- **Award type:** 1
- **Project period:** 2022-04-12 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445377

## Citation

> US National Institutes of Health, RePORTER application 10445377, Intratumoral Cytokine Immunotherapy Studies in Companion Canine Cancer Models (1R01CA271243-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445377. Licensed CC0.

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