# Noninvasive monitoring of therapeutic response to immune checkpoint inhibitors using circulating exosomes in non-small cell lung cancer

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $204,520

## Abstract

Summary/ Abstract: The emergence of immune checkpoint blockade (ICB) therapy has revolutionized the
treatment for advanced cancers including lung cancer. Particularly, anti-PD-1/PD-L1 therapy shows promising
therapeutic outcomes, and some of these therapies are employed as the first line treatment of patients with
metastatic NSCLC. However, not all patients benefit from ICB and some of patients who initially respond to ICB
develop acquired resistance and sometimes. multisystem immune-related adverse events. Thus, it is critically
important to accurately identify and predict lung cancer patients who will respond to ICB before and during a
course of treatment. Here, we propose an innovative screening strategy aiming at early prediction and real-time
monitoring of responders and non-responders to ICB for lung cancer patients. This approach is based on the
isolation, detection, and characterization of circulating exosomes specifically associated with anticancer immune
response rather than analyzing total pool of exosomes. Exosomes are secreted nano-sized particles containing
nucleic acid, protein, and lipid cargo specific to the cell of origin, which are considered as a mirror of the parental
cells. Besides, they can be easily extracted from biofluids as a source of biomarkers of disease status and
treatment response. Herein, we seek to specifically analyze two population of circulating exosomes including
tumor-derived exosomes (TEXs) and PD-L1+ exosomes that serve as the invaluable determinants of the status
of tumor burden and anticancer-immune activity, respectively. We have formulated two Specific Aims that hinge
on developing technologies to achieve our goals: Aim1 will develop a highly sensitive and selective sensing
platform for quantitative analysis of TEXs and PD-L1+ exosomes followed by molecular analysis of TEXs to
explore the molecular signatures associated with treatment outcome. For that, we will genetically engineer novel
bioluminescence-based probes by fusing bioluminescence proteins with tumor-specific and PD-L1-specific
targeting molecules, respectively. Aim 2 will evaluate circulating exosomes from serum of NSCLC patients
treated with ICB therapy. The platform developed in Aim 1 will be used for the quantitative analysis of TEXs and
PD-L1+ exosomes during the treatment, and whether the observed changes can be utilized as a predictive
marker for early identification and monitoring of responders and non-responders to ICB. The circulating TEXs
will be subsequently isolated; their exosomal transcripts, and long non-coding RNAs will be characterized by
using next-generation sequencing to explore the molecular signatures associated with therapeutic outcome. We
will apply computational approaches for data integration, analysis, and interpretation based on the number of
TEXs, expression level of exosomal PD-L1, molecular signatures of TEXs, and patient’s clinical features. In sum,
our project is highly translational and could have a signif...

## Key facts

- **NIH application ID:** 10890842
- **Project number:** 5R21CA283881-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sylvia Daunert
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,520
- **Award type:** 5
- **Project period:** 2023-07-19 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890842

## Citation

> US National Institutes of Health, RePORTER application 10890842, Noninvasive monitoring of therapeutic response to immune checkpoint inhibitors using circulating exosomes in non-small cell lung cancer (5R21CA283881-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890842. Licensed CC0.

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