2. Academic Validation
  3. Bispecific T-cell engagers non-covalently decorated drug-loaded PEGylated nanocarriers for cancer immunochemotherapy

Bispecific T-cell engagers non-covalently decorated drug-loaded PEGylated nanocarriers for cancer immunochemotherapy

  • J Control Release. 2022 Apr:344:235-248. doi: 10.1016/j.jconrel.2022.03.015.
Wei-Jie Cheng 1,  Kuo-Hsiang Chuang 2,  Yu-Ju Lo 3,  Michael Chen 4,  Yi-Jou Chen 5,  Steve R Roffler 6,  Hsiu-O Ho 7,  Shyr-Yi Lin 8,  Ming-Thau Sheu 9
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 2 PhD Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 3 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 4 Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 5 Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 6 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan,. Electronic address: [email protected].
  • 7 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 8 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
  • 9 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
PMID: 35288168 DOI: 10.1016/j.jconrel.2022.03.015
Abstract

Immunotherapy is blooming in recent years. However, this therapy needs to overcome off-target effects, cytokine release syndrome, and low responses in the 'cold' tumor environment. Herein, various combinations of immunotherapies and chemotherapies were proposed to transform 'cold' tumors into 'hot' tumors to enhance the efficacy of immunotherapies. In this study, we prepared a biocompatible ganetespib (GSP)-loaded PEGylated nanocarriers (NCs) with a thin-film method, which exhibited a small particle size (~220.6 nm), high drug loading (~5.8%), and good stability. We designed and produced the cluster of differentiation 3 (CD3)/programmed death ligand 1 (PD-L1)/methoxy-polyethylene glycol (mPEG) trispecific antibodies (TsAbs) as bispecific T-cell engagers (BiTEs) to non-covalently bind the GSP-NCs via anti-mPEG fragment and endowed the GSP-NCs with a targeting ability and immunotherapeutic potential to activate cytotoxic T cells. Decoration of the GSP-NCs with TsAbs (BiTEs-GSP-NCs) significantly promoted the cellular uptake and showed synergistic effects through respective anti-PD-L1 and anti-CD3 activation of T cell-mediated cytotoxicity. In vivo tumor-inhibition studies also showed that the BiTEs-GSP-NCs could inhibit tumor growth with the GSP chemodrug and increase T-cell infiltration. This study provides a promising drug delivery strategy for Cancer immunochemotherapy.

Keywords

Bispecific T-cell engager; Ganetespib; Immune checkpoint; Immunotherapy; Nanocarriers.

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