# Radiation and checkpoint blockade for cancer immune therapy

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $2,263,439

## Abstract

The long-term goal of this P01 is to understand the intersection of radiation biology and cancer immunology
and to translate this research into better therapies with curative potential for patients with cancer. Radiation
therapy (RT) can systemically impact the immune system, and recent clinical success of PD1 and CTLA4
immune checkpoint blockade (ICB) has given rise to our overarching hypothesis that the immune stimulatory
effects of RT can expand the spectrum of clinical responsiveness when combined with dual ICB across
multiple histologies. Our preliminary data and investigative approach bridges studies in both patients and
animal models. To achieve our goals, we have developed three Projects, which require close coordination of
projects and cores. In Project 1, we will determine the clinical and immunological impact of treating patients on
two clinical trials: (i) nivolumab (PD1 mAb) and ipilimumab (CTLA4 mAb) with or without hypofractionated RT
(HFRT) in a randomized phase II study in metastatic melanoma; and (ii) and tremelimumab (CTLA4 mAb) and
durvalumab (PDL1 mAb) with HFRT at two dose schedules in metastatic pancreatic, lung, and breast
carcinoma. In Project 2, we will determine the role of RT in establishing cancer immunity, evaluating the
mechanism of anti-viral signaling through pattern recognition receptors and non-coding RNA and examining
dendritic cell biology and CD40 activation. In Project 3, we will define the genetic and epigenetic basis of
resistance to RT and ICB and examine PDL1 independent pathways to overcome this. Biomarkers revealed in
Projects 2 and 3 will be examined using human samples from the clinical trials in Project 1. The Cores for this
P01 are essential for our progress including provision of administration support for collaboration (Core A), a
state-of-the-art platform for small animal radiation (Core B), and bioinformatics and biostatistical approaches to
drive deep learning from data generated in all Projects (Core C). The potential for paradigm shifting impact
is to transform the indication of RT from “local therapy” to key part of a novel “systemic” immune
therapy for meaningful efficacy against metastatic and advanced cancer.

## Key facts

- **NIH application ID:** 10360418
- **Project number:** 5P01CA210944-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ANDY J MINN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,263,439
- **Award type:** 5
- **Project period:** 2017-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360418

## Citation

> US National Institutes of Health, RePORTER application 10360418, Radiation and checkpoint blockade for cancer immune therapy (5P01CA210944-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360418. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*