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Recent Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Engineering Strategies for Precise Strike Therapy

Chae Eun Lee1, Kyung Mu Noh1, Sungjun Kim1

  • 1Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea.

Biomaterials Research
|March 20, 2025
PubMed

Insights

Developing advanced drug delivery systems, like living cell carriers, can overcome limitations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for effective cancer therapy. These platforms enhance TRAIL

Area of Science:

  • Biomedical Engineering
  • Cancer Therapeutics
  • Drug Delivery Systems

Background:

  • Protein-based therapeutics like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) show promise for selective cancer cell apoptosis.
  • TRAIL targets death receptors DR4 and DR5, highly expressed on cancer cells, sparing healthy tissues.
  • Clinical application of TRAIL is hindered by short half-life, instability, and poor tumor site delivery.

Purpose of the Study:

  • To review novel strategies for developing TRAIL delivery platforms to overcome current therapeutic limitations.
  • To explore biomaterial-mediated carriers, genetically modified cellular products, and cell surface engineering for TRAIL delivery.
  • To discuss clinical translation considerations and future directions for TRAIL-based cancer therapeutics.

Main Methods:

  • Design of biomaterial-mediated carriers with optimized materials, composition, formulation, and surface modulation for enhanced targeting.
  • Development of genetically modified cellular products for increased TRAIL secretion into tumor microenvironments.
  • Application of cell surface engineering for TRAIL immobilization onto infusible cell populations.

Main Results:

  • Living cell-based carriers demonstrate potential for systemic administration and capturing circulating tumor cells, preventing metastasis.
  • Optimized biomaterial carriers enhance targeting efficacy and drug delivery.
  • Engineered cells can augment TRAIL secretion and immobilization for improved therapeutic outcomes.

Conclusions:

  • Novel TRAIL delivery platforms, particularly living cell-based carriers, offer significant advantages for cancer treatment.
  • Addressing challenges in material optimization, genetic modification, and cell engineering is crucial for clinical translation.
  • Future research should focus on complementary strategies to advance TRAIL-based cancer therapeutics.

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