Details

Autor(en) / Beteiligte

• Liu, Jiaying
• Toy, Randall
• Vantucci, Casey
• Pradhan, Pallab
• Zhang, Zijian
• Kuo, Katie M
• Kubelick, Kelsey P
• Huo, Da
• Wen, Jianguo
• Kim, Jinhwan
• Lyu, Zhiheng
• Dhal, Simran
• Atalis, Alexandra
• Ghosh-Choudhary, Shohini K
• Devereaux, Emily J
• Gumbart, James C
• Xia, Younan
• Emelianov, Stanislav Y
• Willett, Nick J
• Roy, Krishnendu

Titel

Bifunctional Janus Particles as Multivalent Synthetic Nanoparticle Antibodies (SNAbs) for Selective Depletion of Target Cells

Ist Teil von

• Nano letters, 2021-01, Vol.21 (1), p.875-886

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Monoclonal antibodies (mAb) have had a transformative impact on treating cancers and immune disorders. 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.