# Brachytherapy to achieve in situ cancer vaccination

> **NIH NIH F30** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $41,540

## Abstract

Project Summary/Abstract
We aim to improve the cure rates for metastatic cancers. To achieve this we propose a combined modality
approach to stimulate and diversify an endogenous anti-tumor immune response capable of recognizing and
destroying metastatic cancers in a manner that will prevent recurrence and enable long-term cancer free
survival. Our intention is to develop a strategy that will overcome current challenges that limit the role of
immunotherapy. Immune checkpoint inhibitors (ICI; e.g. anti-PD-L1), are a class of immunotherapies that
modulate immune tolerance of a tumor by blocking specific inhibitory receptor-ligand interactions on the
surface of T cells and thereby overcoming T cell inhibition or exhaustion. In patients with immunologically “hot”
tumors, characterized by a pre-existing but exhausted anti-tumor immune response, ICIs can restore efficacy
to the anti-tumor immune response, sometimes resulting in complete and durable tumor regression even in
settings of advanced metastatic disease. However, ICIs have not shown clinical benefit in the treatment of
immunologically “cold” cancers that are characterized by low levels of T cell infiltrate and low mutation burden
resulting in few mutation-created neo-antigens. Further, patients with immunologically hot tumors that initially
respond to ICI therapy often show signs of disease progression over time. To improve the extent and duration
of response to ICIs in patients with immunologically “hot” tumors and to prime a de novo anti-tumor immune
response in patients with “cold” tumors, we propose to combine systemic delivery of ICIs with local delivery of
a heterogeneous dose of radiation administered using brachytherapy (BT) at a single tumor with the intent of
stimulating an in situ vaccine effect. To date, nearly all approaches to combining radiation and immunotherapy have
used external beam radiotherapy (EBRT) which delivers a homogenous dose of radiation. Preclinical studies indicate
that the immunogenic effects of radiation are sensitive to dose and field size. Due to its unmatched conformality
and dose heterogeneity, BT may confer meaningful advantages over EBRT when it comes to priming an in
situ vaccine effect. Our broad hypothesis is that a heterogeneous dose of radiation delivered by BT will allow
enhanced activation of multiple dose-dependent immune effects in a single tumor and will elicit a superior in
situ vaccine effect in combination with systemically administered immunotherapies compared to homogeneous
radiation. In a project that builds upon the ongoing collaborative progress of the Morris and McNeel labs, we
will now determine the potency of combining BT with immunotherapy to enhance the immune response against
immunologically cold tumors. In murine models, we will: 1) expand on preliminary data showing potent synergy
with the combination of BT and ICI, 2) use the inherent dose heterogeneity of BT to characterize dose
dependent effects of radiation in a single tumor ...

## Key facts

- **NIH application ID:** 10328489
- **Project number:** 5F30CA250263-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Justin Charles Jagodinsky
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,540
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328489

## Citation

> US National Institutes of Health, RePORTER application 10328489, Brachytherapy to achieve in situ cancer vaccination (5F30CA250263-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328489. Licensed CC0.

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