# Novel Nano-immunotherapy for Treatment of Non-small Cell Lung Cancer

> **NIH NIH R44** · PDX PHARMACEUTICALS, INC. · 2021 · $378,030

## Abstract

Treatment of non-small cell lung cancer (NSCLC) typically, which requires a combination of many highly toxic
drugs and radiation therapy, is not curative. Immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 are
causing a paradigm shift in NSCLC treatment, yet the 5-year survival rate remains below 20%.
This Fast-Track SBIR application aims to develop a novel nano-immunotherapy (termed ARAC - Antigen
Release Agent and Checkpoint Inhibitor) that can greatly improve the efficacy of ICIs leading to curative
outcomes for NSCLC patients. ARAC is built upon our core nanoparticle platform capable of co-delivering
multiple therapeutic agents, while keeping a small size in saline (100 nm), suitable for infusion and tumor
accumulation. The proposed ARAC-02 will co-deliver a polo-like kinase 1 (PLK1)-targeted therapy (volasertib),
a PD-L1 antibody, and the immune-stimulant CpG. Volasertib 1) selectively kills cancer cells, 2) modulates the
immune-suppressive tumor microenvironment, and 3) upregulates PD-L1 expression in cancer cells, providing
opportunity for targeted delivery with PD-L1 antibody on the nanoparticles. CpG is an oligonucleotide that
enhances antigen presentation to generate tumor-specific T cells. The nanoparticles contain a very high
surface density of PD-L1 antibodies (two thousand per particle), which promotes binding to PD-L1 molecules
on cancer cells, followed by internalization and PD-L1 degradation (as effective as 30-fold free PD-L1
antibody), releasing the brakes and allowing T cells to attack the cancer. When given intravenously to mice
bearing lung tumors, the nanoparticle co-delivering volasertib and PD-L1 antibody reduced the necessary dose
for efficacy of each drug by 5-fold. Adding CpG to the nanoconstructs triggers greater adaptive anti-cancer
immunity in a bilateral NSCLC mouse model, leading to complete cures for some mice. The platform was also
found to be safe in monkeys.
In Phase I (Aim 1), ARAC-02 will be optimized for loading of volasertib, PD-L1 antibody, and CpG. Materials
will be screened for size, targeting specificity, efficacy in NSCLC cells, and efficacy and safety in mice.
In Phase II, the pharmacokinetic, biodistribution, efficacy, and safety of the optimal ARAC-02 will be assessed,
both alone (Aim 2) and in combination with the current first-line immunotherapy (Aim 3). Clinically relevant
orthotopic NSCLC mouse models that are resistant to ICIs will be utilized, and findings will be validated in
humanized mice bearing two different patient-derived tumors that represent heterogeneous NSCLC in patients.
The free drugs, single-drug-loaded nanoparticles, and first-line immunotherapy will be used as benchmarks.
Due to its unique ability to stimulate various steps of the adaptive immune response, ARAC-02 is anticipated to
provide curative outcomes, especially when used with current ICIs for complete blockade. ARAC-02 can
upregulate PD-L1 levels thereby promoting efficacy in a broad range of tumor types regardle...

## Key facts

- **NIH application ID:** 10395367
- **Project number:** 1R44CA265751-01A1
- **Recipient organization:** PDX PHARMACEUTICALS, INC.
- **Principal Investigator:** Worapol Ngamcherdtrakul
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,030
- **Award type:** 1
- **Project period:** 2021-09-23 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395367

## Citation

> US National Institutes of Health, RePORTER application 10395367, Novel Nano-immunotherapy for Treatment of Non-small Cell Lung Cancer (1R44CA265751-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10395367. Licensed CC0.

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