Fusion to an albumin-binding domain with a high affinity for albumin extends the circulatory half-life and enhances the in vivo antitumor effects of human TRAIL

Li, Rui; Yang, Hao; Jia, Dianlong; Nie, Qianxue; Cai, Huawei; Fan, Qi-Wen; Wan, Lin; Li, Lin; Lu, Xiaofeng

doi:10.1016/j.jconrel.2016.03.004

Cited by 73 publications

(56 citation statements)

References 38 publications

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“…These results demonstrated that the Z PDGFRβ affibody was tumor-homing, suggesting that tumor-targeted delivery of hTRAIL might be achieved by fusion to the Z PDGFRβ affibody. Previous studies demonstrated that fusion at the N-terminus has less influence on the biological activity of hTRAIL 16,40. Therefore, we produced Z-hTRAIL by fusing the Z PDGFRβ affibody to the N-terminus of hTRAIL.…”

Section: Discussionmentioning

confidence: 99%

“…The plasmid pQE30-hTRAIL containing the gene encoding hTRAIL (aa 114 to 281, accession number BC032722.1) was used to produce hTRAIL according to our previous work 16. To produce the Z PDGFRβ affibody, the unique C-terminal cysteine residue of Z09591 29 was deleted.…”

Section: Methodsmentioning

confidence: 99%

“…On one hand, a short half-life might contribute to the poor clinical efficacy of hTRAIL. PEGylation 13, Fc fusion 14, albumin-fusion 15 and albumin-binding 16 have been used to improve the pharmacodynamics of hTRAIL. On the other hand, decoy receptors 1 and 2 (DcR1 and DcR2), which do not trigger apoptosis upon ligand engagement, are ubiquitously expressed on normal cells 17.…”

Section: Introductionmentioning

confidence: 99%

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Targeted Delivery to Tumor-associated Pericytes via an Affibody with High Affinity for PDGFRβ Enhances the in vivo Antitumor Effects of Human TRAIL

Tao¹,

Yang²,

Shi³

et al. 2017

Theranostics

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Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) has exhibited superior in vitro cytotoxicity in a variety of tumor cells. However, hTRAIL showed a disappointing anticancer effect in clinical trials, although hTRAIL-based regimens were well tolerated. One important reason might be that hTRAIL was largely trapped by its decoy receptors, which are ubiquitously expressed on normal cells. Tumor-targeted delivery might improve the tumor uptake and thus enhance the antitumor effect of hTRAIL. Platelet-derived growth factor receptor β (PDGFRβ)-expressing pericytes are enriched in tumor tissues derived both from patients with colon cancer and from mice bearing colorectal tumor xenografts. A ZPDGFRβ affibody showed high affinity (nM) for PDGFRβ and was predominantly distributed on tumor-associated PDGFRβ-positive pericytes. Co-administration with the ZPDGFRβ affibody did not significantly enhance the antitumor effect of hTRAIL in mice bearing tumor xenografts. Fusion to the ZPDGFRβ affibody endows hTRAIL with PDGFRβ-binding ability but does not interfere with its death receptor binding and activation. The fused ZPDGFRβ affibody mediated PDGFRβ-dependent binding of hTRAIL to pericytes. In addition, hTRAIL bound on pericytes could kill tumor cells through juxtatropic activity or exhibit cytotoxicity in tumor cells after being released from pericytes. Intravenously injected hTRAIL fused to ZPDGFRβ affibody initially accumulated on tumor-associated pericytes and then diffused to the tumor parenchyma over time. Fusion to the ZPDGFRβ affibody increased the tumor uptake of hTRAIL, thus enhancing the antitumor effect of hTRAIL in mice bearing tumor xenografts. These results demonstrate that pericyte-targeted delivery mediated by a ZPDGFRβ affibody is an alternative strategy for tumor-targeted delivery of anticancer agents.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted Delivery to Tumor-associated Pericytes via an Affibody with High Affinity for PDGFRβ Enhances the in vivo Antitumor Effects of Human TRAIL

Tao¹,

Yang²,

Shi³

et al. 2017

Theranostics

Self Cite

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“…Moreover, on cancer cell membranes, there are a number of death receptors (e.g., DR4, DR5), which can be activated by specific proteins, typically by tumor necrosis factor (TNF)‐related apoptosis inducing ligand (TRAIL) or Apo‐2 ligand, to induce cell apoptosis. Delivery of TRAIL protein to targeted cancer cells by TRAIL‐containing nanoparticles (e.g., liposomes, inorganic nanomaterials, polymeric nanoparticles, albumin nanoparticles, etc.) or TRAIL–antibody conjugates has shown great significance in cancer therapy.…”

Section: Therapeutic Strategies Toward Specific Subcellular Compartmentsmentioning

confidence: 99%

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

2018

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Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non-drug-loaded nanoformulations (i.e., metal nanoparticles and molecular self-assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included. According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task-specific applications by integrating specific materials, ligands, as well as methods. In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle-targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects. Finally, the related challenges of critical re-evaluation of this emerging field are presented.

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“…Because of the longer circulatory half-life of ABD fused TRAIL, ABD-TRAIL mediated killing of CTC was significantly longer as evidenced by remarkably reduced secondary lung cancer development. 146 …”

Section: Recent Advances In Trail Therapies Designs and Potential Rolmentioning

confidence: 99%

Journey of TRAIL from bench to bedside and its potential role in immuno-oncology

Naoum¹,

Buchsbaum

Tawadros

et al. 2017

Oncol Rev

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Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies have been developed and being tested pre-clinically and clinically both as a single agent and in combinations. Of note, the monoclonal antibodies were not the only type of antibodies developed to target TRAIL receptors. Recent technology has brought forth several single chain variable domains (scFv) designs fused recombinantly to TRAIL as well. Also, it is becoming progressively more understandable that field of nanotechnology has revolutionized cancer diagnosis and therapy. The recent breakthroughs in materials science and protein engineering have helped considerably in strategically loading drugs into nanoparticles or conjugating drugs to their surface. In this review we aim to comprehensively highlight the molecular knowledge of TRAIL in the context of its pathway, receptors and resistance factors. We also aim to review the clinical trials that have been done using TRAIL based therapies and to review various scFv designs, the arsenal of nano-carriers and molecules available to selectively target tumor cells with TRAIL.

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Fusion to an albumin-binding domain with a high affinity for albumin extends the circulatory half-life and enhances the in vivo antitumor effects of human TRAIL

Cited by 73 publications

References 38 publications

Targeted Delivery to Tumor-associated Pericytes via an Affibody with High Affinity for PDGFRβ Enhances the in vivo Antitumor Effects of Human TRAIL

Targeted Delivery to Tumor-associated Pericytes via an Affibody with High Affinity for PDGFRβ Enhances the in vivo Antitumor Effects of Human TRAIL

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

Journey of TRAIL from bench to bedside and its potential role in immuno-oncology

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