TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer

Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apo...

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Bibliographic Details
Published in:Journal of controlled release 2016-02, Vol.223, p.215-223
Main Authors: Wayne, Elizabeth C., Chandrasekaran, Siddarth, Mitchell, Michael J., Chan, Maxine F., Lee, Rachel E., Schaffer, Chris B., King, Michael R.
Format: Article
Language:English
Subjects:
adhesion
Animals
apoptosis
blood flow
Circulating tumor cells
E-Selectin - administration & dosage
E-Selectin - therapeutic use
Humans
leukocytes
Leukocytes - metabolism
ligands
Liposomes
Male
Metastasis
mice
Mice, Transgenic
Nanomedicine
neoplasm cells
Neoplasm Metastasis - prevention & control
Neoplastic Cells, Circulating - drug effects
prognosis
prostatic neoplasms
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
TNF-Related Apoptosis-Inducing Ligand - administration & dosage
TNF-Related Apoptosis-Inducing Ligand - therapeutic use
TRAIL
Xenograft Model Antitumor Assays
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Summary:Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2015.12.048