Journal
NANO LETTERS
Volume 21, Issue 1, Pages 875-886Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c04833
Keywords
monoclonal antibody; Janus nanoparticle; myeloid-derived suppressor cell; antibody-dependent cellular responses; immunotherapy
Categories
Funding
- Georgia Tech Foundation through the Robert A. Milton Chaired Professorship
- Georgia Institute of Technology
- Children and Athletes Regenerative Medicine Foundation [12456J4]
- Giglio Breast Cancer Innovation Fund [1255d06]
- National Science Foundation [ECCS-2025462]
- U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
- National Institutes of Health [R01-GM123169]
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SNAbs are a synthetic, multivalent Janus nanotherapeutic platform that efficiently targets and depletes myeloid-derived immune-suppressor cells (MDSCs) in mouse-tumor and rat-trauma models. Injection of MDSC-targeting SNAbs in a mouse triple-negative breast cancer model successfully depletes circulating MDSCs, allowing enhanced infiltration of T cells and Natural Killer cells into tumors.
Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune disorders. SNAbs However, their use is limited by high development time and monetary cost, manufacturing complexities, suboptimal pharmacokinetics, and availability of disease-specific targets. To address some of these challenges, we developed an entirely synthetic, multivalent, Janus nanotherapeutic platform, called Synthetic Nanoparticle Antibodies (SNAbs). SNAbs, with phage-display-identified cell-targeting ligands on one face and Fc-mimicking ligands on the opposite face, were synthesized using a custom, multistep, solid-phase chemistry method. SNAbs efficiently targeted and depleted myeloid-derived immune-suppressor cells (MDSCs) from mouse-tumor and rat-trauma models, ex vivo. Systemic injection of MDSC-targeting SNAbs efficiently depleted circulating MDSCs in a mouse triple-negative breast cancer model, enabling enhanced T cell and Natural Killer cell infiltration into tumors. Our results demonstrate that SNAbs are a versatile and effective functional alternative to mAbs, with advantages of a plug- and-play, cell-free manufacturing process, and high-throughput screening (HTS)-enabled library of potential targeting ligands.
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