First-in-human study of 23ME-00610, an antagonistic antibody for genetically validated CD200R1 immune checkpoint, in participants with advanced solid malignancies.

Purpose: In this Phase 1 portion of a first-in-human Phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics, and pharmacodynamics. Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.

Patients And Methods: Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks using an accelerated titration design followed by a traditional 3+3 design, with an initial dose level of 2 mg.

Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure.

Neurotoxicity of an Hepatitis B Virus (HBV) Transcript Inhibitor in 13-Week Rat and Monkey Studies.

The nonclinical safety profile of GS-8873, a hepatitis B virus RNA transcript inhibitor was evaluated in rat and monkey 13-week toxicity studies with 8-week recovery phases. Vehicle or GS-8873 was dosed orally for 13 weeks at 2, 6, 20, and 60 mg/kg/day to Wistar Han rats and at 0.5, 1.

Synthesis and Characterization of Cetuximab-Docetaxel and Panitumumab-Docetaxel Antibody-Drug Conjugates for EGFR-Overexpressing Cancer Therapy.

The safety and efficacy of anticancer antibody-drug conjugates (ADCs) depend on the selection of tumor-targeting monoclonal antibody (mAb), linker, and drug, as well as their specific chemical arrangement and linkage chemistry. In this study, we used a heterobifunctional cross-linker to conjugate docetaxel (DX) to cetuximab (CET) or panitumumab (PAN). The resulting ADCs were investigated for their in vitro EGFR-specific cytotoxicity and in vivo anticancer activity.

Immuno-PET imaging of tumor-infiltrating lymphocytes using zirconium-89 radiolabeled anti-CD3 antibody in immune-competent mice bearing syngeneic tumors.

The ability to non-invasively monitor tumor-infiltrating T cells in vivo could provide a powerful tool to visualize and quantify tumor immune infiltrates. For non-invasive evaluations in vivo, an anti-CD3 mAb was modified with desferrioxamine (DFO) and radiolabeled with zirconium-89 (Zr-89 or 89Zr). Radiolabeled 89Zr-DFO-anti-CD3 was tested for T cell detection using positron emission tomography (PET) in both healthy mice and mice bearing syngeneic bladder cancer BBN975.

The Interplay of Antigen Affinity, Internalization, and Pharmacokinetics on CD44-Positive Tumor Targeting of Monoclonal Antibodies.

Monoclonal antibodies (mAbs) offer promise as effective tumor targeting and drug delivery agents for cancer therapy. However, comparative biological and clinical characteristics of mAbs targeting the same tumor-associated antigen (TAA) often differ widely. This study examined the characteristics of mAbs that impact tumor targeting using a panel of mAb clones specific to the cancer-associated cell-surface receptor and cancer stem cell marker CD44.

The flipped classroom: a course redesign to foster learning and engagement in a health professions school.

Recent calls for educational reform highlight ongoing concerns about the ability of current curricula to equip aspiring health care professionals with the skills for success. Whereas a wide range of proposed solutions attempt to address apparent deficiencies in current educational models, a growing body of literature consistently points to the need to rethink the traditional in-class, lecture-based course model. One such proposal is the flipped classroom, in which content is offloaded for students to learn on their own, and class time is dedicated to engaging students in student-centered learning activities, like problem-based learning and inquiry-oriented strategies.

Pharmacy student engagement, performance, and perception in a flipped satellite classroom.

Objective: To determine whether "flipping" a traditional basic pharmaceutics course delivered synchronously to 2 satellite campuses would improve student academic performance, engagement, and perception.

Design: In 2012, the basic pharmaceutics course was flipped and delivered to 22 satellite students on 2 different campuses. Twenty-five condensed, recorded course lectures were placed on the course Web site for students to watch prior to class.