# Targeted nanotechnology for the pancreatic tumor immune microenvironment

> **NIH NIH P41** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $208,538

## Abstract

PROJECT SUMMARY: TR&D 2
Cancer can rarely be eradicated with single-agent therapy. More information than is capable of being carried by
one small molecule is often required. We can synthesize nanomedicines engineered to perform multiple tasks
in sequence, leveraging the tumor milieu for initiation of these tasks. For instance, we now have the ability to
design technology meaningful for management of a variety of cancers, including colorectal (CRC), melanoma
and even pancreatic ductal adenocarcinoma (PDAC), one of the most insidious and lethal malignancies. Here
we will develop platform technology to enable treatment of those cancers whether localized or metastatic. The
goal will be to reprogram malignant cells and the related tumor microenvironment (TME) to eradicate tumor in
situ. The nanoparticle (NP) that we will ultimately produce will be optimized with respect to the key properties of
targetability (pharmacokinetics), payload delivery and efficacy. It will be a combination of two separate platforms
optimized for other purposes and previously leveraged for other malignancies. The first platform involves use of
mesoporous silica nanoparticles (MSN), which will be utilized to test two different targeting moieties and a
therapeutic agent, TLY012, while the second uses a poly(beta-amino ester) (PBAE) structure, and is designed
to deliver nucleic acids intracellularly, including for reprogramming the TME. We will use these two different
platforms, and the corresponding experience and new preliminary data, to develop a hybrid particle that
combines the best properties of each. Aims 1 and 2 will be dedicated primarily to the synthesis and testing of
the MSN, which are adept at presenting cell surface molecules and delivering therapeutics upon target
engagement. Aim 3 will involve development of the PBAE NPs for theranostic intracellular delivery of plasmid,
including encoding an immunostimulatory cytokine, while the final aim will be concerned with synthesis, testing
and optimization of the combination NP, designed to overcome both extracellular and intracellular bottlenecks.
We will focus on CRC, which is the second deadliest cancer, melanoma, and PDAC, the third deadliest cancer.
There is a variety of phenotypes associated with PDAC, in particular, which can be primarily cystic, mucinous,
or can be fenced in behind a desmoplastic stroma. We are excited to pursue PDAC because we have shown
that TLY012 can reprogram the TME to decrease desmoplasia and increase cytotoxic T cell infiltration.

## Key facts

- **NIH application ID:** 10848984
- **Project number:** 2P41EB024495-06A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MARTIN G POMPER
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $208,538
- **Award type:** 2
- **Project period:** 2017-09-15 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848984

## Citation

> US National Institutes of Health, RePORTER application 10848984, Targeted nanotechnology for the pancreatic tumor immune microenvironment (2P41EB024495-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10848984. Licensed CC0.

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