# Single Vesicle Phenotyping of Circulating Exosomes Carrying Immunomodulatory Markers for Therapy Selection and Monitoring.

> **NIH NIH R43** · NANOVIEW DIAGNOSTICS, INC. · 2021 · $351,922

## Abstract

ABSTRACT
Over the past decade, immunotherapy has recruited the patients’ own immune system in the fight against the
tumor. In particular, the successful blocking of the interaction between programmed cell death-1 (PD-1) and its
ligand PD-L1 has paved the way for the development of new treatments for several of the most devastating
cancers. In cancers such as non-small cell lung cancer (NSCLC), upregulation of PD-L1, both in the tumor cells
and in macrophages, reduces the host’s immune response, thereby enhancing tumor aggressiveness. While
PD-1/PD-L1 checkpoint-blockade immunotherapy has become a real ‘game-changer’ for many cancer patients,
response rates remain relatively low, ranging from 15 to 40%, depending on the type of cancer and the stage of
the disease.
The current assessment of whether a patient should be treated with PD-1/PD-L1 blockade therapy is based on
expression levels of PD-L1 and degree of tumor-infiltrating immune cells using immunohistochemistry (IHC).
This approach has significant downsides: 1) samples are surgically obtained, posing additional risk, and
potentially triggering enhanced metastasis as a result of primary tumor perforation; and 2) these measures are
rarely sensitive or specific enough in predicting response efficacy, being prone to generating false-positive
results. In addition, IHC lacks a clean and quantitative definition of what threshold defines a PD-L1 positive
tumor. It was shown that subsets of patients do not benefit from checkpoint-blockade immunotherapy despite
testing positive for PD-L1 expression using IHC, and conversely, a significant number of patients responded well
to it, despite testing negative for PD-1/PD-L1 in IHC-based tests. To spare patients from ineffective therapy and
limit the number of those exposed to potential autoimmune side effects, the search for a reliable predictive
biomarker allowing patient selection of those who would benefit from anti-PD-1/PD-L1 therapy has become
more urgent than ever.
In this proposal, we will use our ExoView technology to create an assay able to identify and quantify circulating
exosomes that carry PD-L1. Exosomes have been shown to play a critical role in many pathologies and more
recently in anti-tumor immunity. Furthermore, the vesicular nature of exosomes allows the identification of protein
signatures which in turn may reveal valuable information about the parent cell type. Aim 1 will establish an
antibody able to immobilize exosomes containing PD-L1 and validate the specificity and sensitivity of such
antibodies in human plasma. Aim 2 will quantify PD-L1 positive exosomes originating from immune cells
vs. tumor cells. Using various cellular markers will enable identifying the origin of PD-L1-expressing exosomes.
Aim 3 will focus on Quantification of PD-L1 in vesicles from immune vs tumor cells in NSCLC plasma
samples and correlate to PD-L1 IHC score and outcome of anti-PD-1/PD-L1 therapy.

## Key facts

- **NIH application ID:** 10254689
- **Project number:** 1R43CA257433-01A1
- **Recipient organization:** NANOVIEW DIAGNOSTICS, INC.
- **Principal Investigator:** George Daaboul
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $351,922
- **Award type:** 1
- **Project period:** 2021-09-03 → 2022-05-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254689

## Citation

> US National Institutes of Health, RePORTER application 10254689, Single Vesicle Phenotyping of Circulating Exosomes Carrying Immunomodulatory Markers for Therapy Selection and Monitoring. (1R43CA257433-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10254689. Licensed CC0.

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