Publications by authors named "Amanda Shafer"

Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.

Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant.

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Article Synopsis
  • Cytokine release syndrome (CRS) is a common side effect of CAR-T cell therapy, but researchers have developed self-regulating T cells that help reduce its severity by secreting cytokine inhibitors.
  • In preclinical studies using a humanized mouse model, T cells that secrete a modified version of tocilizumab (Toci) showed less CRS-related toxicity and improved safety compared to traditional tocilizumab treatment.
  • Additionally, these Toci-secreting CAR-T cells demonstrated better antitumor effects and enhanced the presence of beneficial T-cell types in the tumor microenvironment, indicating a promising strategy for making CAR-T therapy safer and more effective.
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There is a major societal need for analgesics with less tolerance, dependence, and abuse liability. Preclinical rodent studies suggest that bifunctional ligands with both mu (MOPr) and delta (DOPr) opioid peptide receptor activity may produce analgesia with reduced tolerance and other side effects. This study explores the structure-activity relationships (SAR) of our previously reported MOPr/DOPr lead, benzylideneoxymorphone (BOM) with C7-methylene-substituted analogs.

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Chimeric antigen receptors (CAR) are fusion proteins whose functional domains are often connected in a plug-and-play manner to generate multiple CAR variants. However, CARs with highly similar sequences can exhibit dramatic differences in function. Thus, approaches to rationally optimize CAR proteins are critical to the development of effective CAR T-cell therapies.

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The opioid crisis continues to claim many lives, with a particular issue being the ready availability and use (whether intentional or accidental) of fentanyl and fentanyl analogues. Fentanyl is both potent and longer-acting than naloxone, the standard of care for overdose reversal, making it especially deadly. Consequently, there is interest in opioid reversal agents that are better able to counter its effects.

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δ-Opioid receptor (-receptor) agonists produce antihyperalgesia, antidepressant-like effects, and convulsions in animals. However, the role of agonist efficacy in generating different -receptor-mediated behaviors has not been thoroughly investigated. To this end, efficacy requirements for -receptor-mediated antihyperalgesia, antidepressant-like effects, and convulsions were evaluated by comparing the effects of the partial agonist BU48 and the full agonist SNC80 and changes in the potency of SNC80 after -receptor elimination.

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Objectives: To design and implement curricular modifications to a nonprescription therapeutics course to better meet course objectives.

Design: Improvements included the addition of journaling, mastery grading, case studies, verbal examinations, educational mentors, and encouraging classroom participation.

Assessment: Student course evaluations and grades were used to assess the impact of the pedagogical modifications.

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Background: Severe obesity is associated with type 2 diabetes and hypertension. Improvement in these comorbidities after surgically-induced weight loss has been documented, and laparoscopic adjustable gastric banding (LAGB) is an effective weight loss operation.

Methods: Of 840 patients who underwent Lap-Band, data are available in 402 out of 413 patients whose surgery took place at >/= 1 year ago.

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