# Synthetic Nanoparticle-antibody (SNAb) Based Depletion of Myeloid-Derived Suppressor Cells for TB Host-Directed Therapy

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $836,957

## Abstract

ABSTRACT
In patients with tuberculosis (TB), detrimental immune responses to Mycobacterium tuberculosis (Mtb) infection
dominate over beneficial immunity, resulting in uncontrolled Mtb replication, lung granulomas and progression
to TB disease. Immunosuppressive pathways induced by Mtb promote lung pathology and tissue damage and
prevent protective immune responses. This suboptimal lung microenvironment can also interfere with antibiotic-
mediated killing of Mtb. Therefore, in-depth understanding of immunosuppressive mechanisms during TB is
critical for developing novel immunomodulatory therapies that tip the balance away from pathogenic responses
and towards protective immunity and better bacterial clearance. Thus, host-directed therapies (HDT) that target
immunosuppressive pathways in conjunction with anti-TB antibiotics have the potential to improve TB treatment.
Recent studies show that a population of immature myeloid cells that are recruited to the lung after Mtb infection
contribute to immunosuppression during TB. These cells, termed myeloid-derived suppressor cells (MDSCs),
were first described in cancer as negatively regulating tumor microenvironments and suppressing NK cell and T
cell cytotoxic functions. Interestingly, accumulation of MDSCs correlates with TB disease pathology and these
cells can also harbor Mtb intracellularly. However, in contrast to cancer, the functions of MDSCs in TB are poorly
understood. We hypothesize that MDSCs prevent beneficial innate and adaptive immune responses to Mtb
infection by suppressing T cell, NK cell and macrophage functions. We further hypothesize that depleting MDSCs
in Mtb-infected mice will enhance immune responses to Mtb in the lung and significantly improve TB treatment
efficacy.
We have developed a versatile and effective approach to deplete MDSCs in the lung via novel multivalent
synthetic nanoparticle antibodies (SNAbs) that specifically target and deplete MDSCs through antibody-like
killing mechanisms. In this MPI-R01 application, we combine expertise in TB pathogenesis and immunology
research (Rengarajan, Emory) with expertise in immuno-engineering and nanotherapeutics (Roy, Georgia-Tech)
to investigate the role of MDSCs in TB disease progression and pathology, and regulating immunity to TB, and
to explore MDSCs as targets of HDT for TB. We will investigate the following Specific Aims: Aim 1. Evaluate
how depleting MDSCs using SNAbs impacts TB disease progression. Aim 2. Investigate how MDSCs suppress
immune responses to Mtb infection. Aim 3. Test the hypothesis that depletion of MDSCs will enhance the
efficacy of anti-TB treatment. Together, these studies will advance our understanding of how MDSCs suppress
immunity to TB and provide insights into MDSCs as targets for adjunctive HDTs.

## Key facts

- **NIH application ID:** 10327084
- **Project number:** 1R01AI155023-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** KRISHNENDU ROY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $836,957
- **Award type:** 1
- **Project period:** 2021-08-05 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327084

## Citation

> US National Institutes of Health, RePORTER application 10327084, Synthetic Nanoparticle-antibody (SNAb) Based Depletion of Myeloid-Derived Suppressor Cells for TB Host-Directed Therapy (1R01AI155023-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327084. Licensed CC0.

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