# Rapid evaluation of immunotherapy regimens in ex vivo human pancreatic tumor slice cultures.

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2022 · $183,261

## Abstract

There is an urgent need to evaluate immunotherapy combination regimens in pre-clinical models that faithfully
represent the complex biology of human pancreatic ductal adenocarcinoma (PDAC) tumors. Since ex vivo
human PDAC tumor slice cultures maintain the tumor morphology, stromal architecture, and immune cell
composition of in vivo PDAC tumors, slice cultures have potential utility in the rapid screening of immunotherapy
combination regimens for PDAC. The main objective in this application is to use human PDAC tumor slice
cultures to identify combination regimens that enhance the response to immune checkpoint inhibitors in PDAC.
The central hypothesis is that human PDAC tumor slice cultures will allow for rapid evaluation and mechanistic
characterization of novel immunotherapy combination regimens against PDAC. Two specific aims are proposed:
1) Screen combination regimens in human pancreatic tumor slice cultures; and 2) Characterize the mechanisms
by which the effective combination therapies promote immune responses in pancreatic tumors. Under the first
aim, novel combination regimens with epigenetic and immune checkpoint inhibitors will be tested in human
PDAC tumor slice cultures using small molecule inhibitors and antibodies that are currently in early phase human
studies. The ability of these regimens to enhance cytolytic CD8+ T cell infiltration and function will be evaluated
to identify the regimens most effective at cancer cell killing. In the second aim, the mechanisms by which the
effective combination regimens successfully overcome immune, biochemical, and physical barriers to CD8+ T
cell infiltration and function will be characterized. The extent to which the effective combination regimens
decrease immunosuppressive cells, cytokines, and chemokines will be evaluated. The extent to which the
effective combination regimens enhance the spatial interaction between CD8+ T cells and cancer cells to
promote successful cancer cell killing will also be evaluated. There are several innovative elements in this
proposal, including the combination of checkpoint inhibitors with small molecule inhibitors that have not been
previously evaluated together, and the use of ex vivo slice cultures of human PDAC tumors to rapidly evaluate
efficacy of immunotherapy regimens. This proposed research is significant because it will have important clinical-
translational implications and should result in the development of mechanism-based novel combination therapies
for PDAC.

## Key facts

- **NIH application ID:** 10312775
- **Project number:** 5R21CA255291-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Hidayatullah G. Munshi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $183,261
- **Award type:** 5
- **Project period:** 2020-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312775

## Citation

> US National Institutes of Health, RePORTER application 10312775, Rapid evaluation of immunotherapy regimens in ex vivo human pancreatic tumor slice cultures. (5R21CA255291-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10312775. Licensed CC0.

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