Publications by authors named "G W Ashley"
Article Synopsis
- IL-15 agonists are promising immunotherapy options as they boost the growth of immune cells like natural killer (NK) and CD8 T cells, but they have a short duration in the body requiring frequent doses.
- A new approach using hydrogel microspheres (MS) was developed to extend the half-life of IL-15, which successfully increased its duration to about one week.
- The study found that the MS conjugate of another IL-15 agonist, RLI, had a shorter half-life of 30 hours and was effective in stimulating immune cells, but caused significant injection-site toxicity; thus, it was focused on for intra-tumoral therapy where such effects could be potentially beneficial.
The objective of this work was to develop a long-acting form of the lipidated peptide semaglutide that can be administered to humans once-monthly. Semaglutide was attached to hydrogel microspheres by a cleavable linker with an expected in vivo release half-life of about 1 mo. After a single subcutaneous dose, the pharmacokinetic parameters of released semaglutide and bodyweight loss were determined in mice, and results were used to estimate the dosing and pharmacokinetics of the released semaglutide in humans.
View Article and Find Full Text PDFParry Romberg syndrome (PRS) is a rare self-limiting disease, typically occurring in children and young adults, that causes slow progressive atrophy of one-half of the face. It primarily affects the subcutaneous tissue and skin with some cases exhibiting deeper extension to glandular, osseous and muscular structures. Neurologic and ocular involvement is variable.
View Article and Find Full Text PDFThe enhanced permeability and retention (EPR) effect controls passive nanodrug uptake in tumors and may provide a high tumor payload with prolonged retention for cancer treatment. However, EPR-mediated tumor uptake and distribution vary by cancer phenotype. Thus, we hypothesized that a companion PET imaging surrogate may benefit EPR-mediated therapeutic drug delivery.
View Article and Find Full Text PDFIntratumoral (IT) therapy is a powerful method of controlling tumor growth, but a major unsolved problem is the rapidity that injected drugs exit tumors, limiting on-target exposure and efficacy. We have developed a generic long acting IT delivery system in which a drug is covalently tethered to hydrogel microspheres (MS) by a cleavable linker; upon injection the conjugate forms a depot that slowly releases the drug and "bathes" the tumor for long periods. We established technology to measure tissue pharmacokinetics and studied MSs attached to SN-38, a topoisomerase 1 inhibitor.
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