174 research outputs found
ASO Author Reflections: Return to Isolated Limb Infusion for In-Transit Melanoma
No full textASO Author ReflectionsMichael J. Carr, Hidde M. Kroon, and Jonathan S. Zage
ASO Author Reflection: Isolated Limb Infusion for Locally Advanced Melanoma in the Extremely Old Patient is Safe and Effective
No full textASO Author reflectionsAbstract unavailableJüri Teras, Hidde M. Kroon and Jonathan S. Zage
Pharmacological Interventions for Improving Adenovirus Usage in Gene Therapy
No full textGene therapy may be an innovative and promising new treatment strategy for cancer but is limited due to a low efficiency and specificity of gene delivery to the target cells. Adenovirus is the preferred gene therapy vector for systemic delivery because of its unparalleled in vivo transduction efficiency. Intravenous administration of low doses of adenovirus results in adenovirus sequestration in the liver due to binding to the scavenger receptor present on Kupffer cells. When the amount of adenovirus surpasses the binding capacity of Kupffer cells, hepatocytes absorb adenovirus particles in a blood factor-dependent manner. Increasing the Ad dose even more will saturate both the Kupffer cells and hepatocytes. Then sinusoid endothelial cells bind adenovirus particles in an RGD motif-dependent manner. Strategies to eradicate the binding to liver cells include drugs to interfere or eliminate binding to specific cell types, adenovirus capsid protein mutations and chemical modifications of adenovirus to shield the capsid proteins from cellular receptors. The combined use of these approaches should ultimately lead to successful systemic application of adenovirus in humans
Targeting of adenoviral gene therapy vectors: the flexibility of chemical and molecular conjugation
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