# Particulate Delivery of STING Agonist as Anti-cancer Immuotherapeutics and Cancer Microbiome

> **NIH NIH K00** · STANFORD UNIVERSITY · 2020 · $30,034

## Abstract

Abstract
Cancer ranks as the second leading cause of death, contributing to nearly 1 in every 4 death in the US. Current
cancer immunotherapies, especially checkpoint blockade, is largely influenced by PD-L1 expression in tumors;
and patients with limited PD-L1 positive expression are normally less responsive to the immunotherapy. These
findings suggest new technologies are needed to for PD-L1 resistant tumors. Cyclic [G(3',5')pA(3',5')p] (cGAMP)
has recently emerged as an exciting new class of vaccine adjuvants, which sequentially activate innate immune
responses and orchestrate adaptive immunity. Tumor associated macrophages (TAMs), a major type of immune
cells in tumor microenvironment, are a potent target for adjuvant therapy. Particulate systems are ideal vehicles
for targeting TAM population within tumor. Additionally, combination therapy holds great promise for tumor
prevention and treatment. Most important, the critical role of cancer microbiome is gaining increased interests
for cancer therapy. We hypothesize that Particulate cGAMP adjuvants targeting TAMs can enhance anti-tumor
immune response and reverse the pro-tumorigenic microenvironment in both PD-L1 responsive and resistant
cancers, and improve the anti-tumor efficiency in combination with checkpoint blockade and tumor resection.
We have tested and will continue to test the hypothesis using B16F10 melanoma (subcutaneous and lung
metastasis models; PD-L1 responsive) and C3(1)Tag basal-like breast cancer (orthotopic and spontaneous GEM
models; PD-L1 resistant), and test the following specific aims: Aim 1. Particulate delivery of STING agonist as
anti-cancer immuotherapeutics: (F99 phase). We optimized liposomal NP and Ace-DEX MP delivery systems
for cGAMP to evaluate the cellular uptake and M2->M1 skewing capacity, and detect major histocompatibility
(MHC) gene and costimulatory gene expression and cytokine production in vitro. We also investigated the tissue
distribution of particulate cGAMPs and their anti-tumor efficacy in above-mentioned tumor models. Aim 2.
Mechanism by which particulate delivery of STING agonist acts an as anti-cancer immuotherapeutic and
combination therapies: (F99 phase). We will study the role of macrophage, CD4+ and CD8+ T cells, and NK
cells in anti-tumor response of particulate cGAMPs. We will also monitor long term survival and tumor recurrence
by combination therapies of particulate cGAMPs with anti-PD-L1 antibodies and tumor resection in above-
mentioned tumor models. Aim 3. The Postdoctoral Research Direction (K00 phase). I will pursue my interest in
understanding the mechanism and functional role of gut microbiota in host response to cancer development and
therapy, meanwhile, with a particular interest in studying the role of oral microbiota in response to head and neck
cancer therapeutics and restoration.

## Key facts

- **NIH application ID:** 9844935
- **Project number:** 5K00CA223019-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ning Cheng
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,034
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844935

## Citation

> US National Institutes of Health, RePORTER application 9844935, Particulate Delivery of STING Agonist as Anti-cancer Immuotherapeutics and Cancer Microbiome (5K00CA223019-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9844935. Licensed CC0.

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