# Delivery of cytokines for cancer immunotherapy using nanolayer-controlled trafficking of liposomal nanoparticles

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $321,799

## Abstract

An immunosuppressive or immune excluded tumor microenvironment (TME) plays a key role in limiting the
response of many tumor types to immunotherapy. One attractive strategy to accomplish increased lymphocyte
infiltration in tumors is the use of cytokines, which can directly impact multiple immune pathways and reprogram
the TME to enable a robust immune response against cancer cells. Unfortunately, despite this obvious potential,
many cytokines have been limited clinically due to toxicity concerns. Rational drug delivery strategies that can
rescue the therapeutic potential of cytokines could act as an important step in our ability to carefully manipulate
the anti-tumor immune response in the TME and open the door for more effective immunotherapies.
Nanoparticles (NPs) are a promising vehicle for the rescue of toxic cytokines. While many studies have used
NPs to improve efficacy and toxicity, there remains a substantial knowledge gap surrounding the role of NP
biophysical properties on enhanced delivery. There is much that is not yet understood about how nanoparticles
traffic and how these differences can affect therapeutic outcomes. We are uniquely positioned to investigate the
role of NP biophysical properties on cytokine delivery given our extensive experience in both NP design for
targeted tumor cell delivery and in polyelectrolyte layer-by-layer (LbL) assembly. LbL-NP systems can be
designed to modulate the release of multiple drugs from the core and from surrounding layers, often with time
dependent staged release; whereas, manipulating the outer layer to possess certain surface chemistries and
targeting moieties can significantly impact trafficking of particles on both the anatomical and cellular level. Using
this system will allow for a systematic investigation of the role of these unique NP properties on effective cytokine
delivery. The goal of this work is to understand and control the delivery of cytokines against solid tumors
using LbL-NPs as a tool, with a focus on the impact of trafficking, localization and release kinetics of the
particle and payload.
Our work will focus on interleukin-12 (IL-12), one of the most potent and toxic proinflammatory cytokines for
which we have recently demonstrated improved efficacy and lowered systemic toxicity by using LbL-NPs that
bind to the surface membrane of ovarian cancer cells. Our studies will take place within the context of advanced
serous ovarian cancer (OC), which has shown limited response to existing immunotherapies, and non-small cell
lung cancers (NCSLC), which is highly responsive, but only for a defined subset of patients. IL-12 loaded NPs
with external layers possessing a range of surface chemistries and targeting moieties will be examined for cellular
and subcellular uptake and immune cell stimulation. Cytokine release kinetics will be examined and optimized,
and nanoparticle systems will be examined in vivo for delivery of cytokines alone and in combination with anti-
PD1 treatment...

## Key facts

- **NIH application ID:** 10187529
- **Project number:** 5R01CA235375-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Paula T Hammond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $321,799
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187529

## Citation

> US National Institutes of Health, RePORTER application 10187529, Delivery of cytokines for cancer immunotherapy using nanolayer-controlled trafficking of liposomal nanoparticles (5R01CA235375-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10187529. Licensed CC0.

---

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