# Molecular Targeted Radionuclide Therapy for Tumor Immunomodulation and Enhancing Immunotherapy Response

> **NIH NIH P01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $2,361,658

## Abstract

PROJECT SUMMARY – OVERALL
This Program Project grant will establish the fully integrated interdisciplinary programs of research and core
facilities that are necessary to develop a fundamental understanding of the complex interplay between two
rapidly emerging fields in cancer therapy: 1) targeted radionuclide therapy (TRT) and 2) immunotherapy. Our
overarching objectives are to develop a detailed mechanistic understanding of the immunomodulatory capacity
of TRT agents and to evaluate and compare the ability of these agents to elicit cooperative therapeutic
interactions in combination with immunotherapies. To achieve this, we will employ a representative variety of
TRT agents to deliver radiation in vivo using clinically relevant murine tumor models and companion canines that
have spontaneously developed cancers. We will determine the precise dosimetry for each radionuclide-, TRT
vector-, and tumor model. This will facilitate studies of dose-, dose-rate-, and dose-range-dependent effects on
the host immune system, tumor infiltrating immune cells, cytokine expression in the tumor microenvironment,
immune susceptibility of tumor cells, mechanisms of immune suppression, and the development of antigen-
specific adaptive immunity. We will determine the functional consequences of these effects by testing the broad
hypothesis that, by modulating tumor immune tolerance and functional immunogenicity at all tumor sites, TRT
will increase response to certain cancer immunotherapies. We will test this in the following Program Projects:
 Project 1: Novel TRTs for Dosimetry-Guided Immunomodulation
Project 2: TRT to enhance tumor cell immune susceptibility and response to immune checkpoint inhibitors
Project 3: Combining TRT with a localized in situ vaccine to overcome immune suppression in the tumor
 microenvironment and augment T cell responses
Project 4: TRT with tumor-specific vaccine to stimulate and expand T-cell activation
These highly integrated projects will not only benefit from the methods and findings generated in one another,
but they also will directly benefit from the expertise and service of four essential Core Facilities: 1) Advanced
imaging and dosimetry core (AIDC), 2) Radiopharmaceutical and radiochemistry core (RPRC), 3) Biostatistics
and bioinformatics core (BBC), and 4) Administrative core. Complementing these are robust institutional facilities
that will enable successful completion of our proposed studies. Our multidisciplinary team brings together the
broad expertise needed to mobilize these resources in pursuit of our proposed objectives. These efforts will
further benefit from robust institutional matching support, leadership of a strong Internal Advisory Committee,
invaluable Industry collaborations, and expertise of an External Advisory Board. Because of the immediate and
broad potential for clinical translation of our results, these studies portend an opportunity to improve the treatment
of any oncology patient, regardless of cancer...

## Key facts

- **NIH application ID:** 10873207
- **Project number:** 5P01CA250972-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Zachary Scott Morris
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,361,658
- **Award type:** 5
- **Project period:** 2020-09-14 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873207

## Citation

> US National Institutes of Health, RePORTER application 10873207, Molecular Targeted Radionuclide Therapy for Tumor Immunomodulation and Enhancing Immunotherapy Response (5P01CA250972-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873207. Licensed CC0.

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