2. Academic Validation
  3. Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy

Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy

  • Sci Adv. 2020 Jul 3;6(27):eaba8564. doi: 10.1126/sciadv.aba8564.
Kin Man Au 1 2,  Steven I Park 3 4,  Andrew Z Wang 1 2
Affiliations

Affiliations

  • 1 Laboratory of Nano- and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 2 Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 4 Levine Cancer Institute, Atrium Health, Division of Hematology and Oncology, 1021 Morehead Medical Dr, Suite 20121, Charlotte, NC 28025, USA.
PMID: 32923587 DOI: 10.1126/sciadv.aba8564
Abstract

Activation of the innate immune system and natural killer (NK) cells has been a key effort in Cancer Immunotherapy research. Here, we report a nanoparticle-based trispecific NK cell engager (nano-TriNKE) platform that can target epidermal growth factor receptor (EGFR)-overexpressing tumors and promote the recruitment and activation of NK cells to eradicate these Cancer cells. Moreover, the nanoengagers can deliver cytotoxic chemotherapeutics to further improve their therapeutic efficacy. We have demonstrated that effective NK cell activation can be achieved by the spatiotemporal coactivation of CD16 and 4-1BB stimulatory molecules on NK cells with nanoengagers, and the nanoengagers are more effective than free antibodies. We also show that biological targeting, either through radiotherapy or EGFR, is critical to the therapeutic effects of nanoengagers. Last, EGFR-targeted nanoengagers can augment both NK-activating agents and chemotherapy (epirubicin) as highly effective Anticancer agents, providing robust chemoimmunotherapy.

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