TRAIL-based gene delivery and therapeutic strategies

  • Acta Pharmacol Sin. 2019 Nov;40(11):1373-1385. doi: 10.1038/s41401-019-0287-8.
Hui-Hai Zhong  1  2 ,  Hui-Yuan Wang  2 ,  Jian Li  1 ,  Yong-Zhuo Huang  3
Affiliations
  • 1. Shanghai University College of Sciences, Shanghai, 200444, China.
  • 2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 3. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].
PMID: 31444476 DOI: 10.1038/s41401-019-0287-8
Abstract

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the Death Receptor 4 (DR4) or DR5, TRAIL induces Apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a Cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of Cancer cells. TRAIL gene transfection can produce a "bystander effect" of tumor cell killing and provide a potential solution to TRAIL-based Cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced Apoptosis, combination therapy of TRAIL DNA with Other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.

Keywords
DNA; TRAIL; cancer therapy; drug delivery systems; gene delivery; gene therapy; non-viral vectors.
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