Mouse versus rabbit: Time course of corneal ocular toxicity of an antibody drug conjugate (ADC) with a maytansinoid payload

ACT 2024 -- Microcystic-like epithelial changes (MECs) in the cornea (keratopathy) are a known ocular toxicity risk of antibody-drug conjugates with microtubulin-acting payloads that generally manifest unrelated to antibody target and occur in the absence of corneal target expression. Dutch-Belted rabbits have been utilized for ocular toxicity studies to replicate and investigate presentation, onset and explore prophylactic techniques to mitigate this corneal finding. Here we evaluate if mice are a useful preclinical model for predicting keratopathy and compare the onset, severity and characterization of MECs in rabbits to mice using confocal microscopy and histopathological evaluation.

Inhaled delivery of a selective immune modulator to minipigs produces favorable toxicity profile

ACT 2024 -- OCI-B2 is a potential therapy for COVID-19 through immune modulation allowing B cell stimulation to fight the virus by inhibiting cascades leading to acute respiratory distress syndrome (ARDS). The first-in-human nonclinical safety assessment package was undertaken using the inhaled route. Inhalation delivery directly to lungs is important due to compromised pulmonary circulation in ARDS. Minipig was identified as the most suitable non-rodent species due to metabolic profiling. Favorable toxicology results enabled progression to Phase I clinical trial.

Bridging the Gap: Enabling Equal Access to Biomarker Cancer Testing and Clinical Trials for Black Patients

Advancements in biomarker testing, clinical research and targeted th­­erapies offer personalized treatment plans that can improve patient health outcomes, but Black patients with cancer often do not have access to these breakthroughs in cancer care. Some of the barriers faced by many Black patients with cancer include lack of insurance coverage, medical biases, medical mistrust and lack of awareness. In particular, this survey found that the main barriers were, in fact, a mistrust in the medical system, a fear for safety and a concern about being a “guinea pig” a test subject for unproven therapies without their knowledge or consent. 

Assessment of leading regulatory T cell immunophenotyping methods using flow cytometry

ACT 2024 -- Regulatory T cells (Tregs) are widely recognized as a critical component of the immune system and an increasing number of studies are identifying new roles these cells play in immune tolerance and the success of clinical immunotherapy treatment. Due to the importance of accurately measuring Tregs in the modern drug development landscape, greater scrutiny is being placed on the methods used to identify them. Immunophenotyping via flow cytometry is a widely recognized technique for analyzing Tregs in whole blood from both preclinical and clinical samples; however, the preferred set of markers for identifying Tregs is debated. Here, our laboratory examined three widely used Treg phenotypes (CD25+FoxP3+, CD25+CD127- and CD25+FoxP3+CD127-) in parallel using whole blood from up to 32 cynomolgus macaques, a common nonhuman primate model in toxicological safety assessment studies. 

Comparison of intratracheal and inhaled AAV pulmonary deposition in two species

ACT 2024 -- Cell and gene therapies (CGT) offer an attractive approach to treating monogenic pulmonary diseases. Standard nonclinical inhalation (INH) exposure systems require greater volumes of test article than other parenteral routes of administration because multiple animals are simultaneously dosed on a single exposure system with innate inefficiencies. Because clinical treatment with CGT modalities will likely only require single or infrequent dose administration, intratracheal (IT) administration offers an alternative route for pulmonary delivery; however, IT dosing requires anesthesia. Customized administration techniques for IT administration to cynomolgus monkey (NHP) and nose-only inhalation to mice were set up for delivery of an adeno-associated virus (AAV). Results from the mouse study were presented previously, while here the hypothesis tested is regarding achieved lung doses and test article usage.

A 29-day two-dose and 3-day one-dose research and development study of intrathecal injection or epidural infusion in rats

ACT 2024 -- Treatment for neurological disorders is widely an unmet need. According to Feigin et al., 15 neurological disorders were identified to be the underlying cause in approximately 9 million global deaths in 2016. Administration directly into the intrathecal (IT) or epidural spaces bypasses the blood-brain barrier to enhance CNS drug distribution and efficacy while reducing systemic drug exposure and side effects. The purpose of this study was to evaluate the tolerability and feasibility of IT injection of Omnipaque 300 and/or artificial cerebral spinal fluid (aCSF) or epidural infusion of Omnipaque 300 and sterile saline in rats.

Development of an electrochemiluminescence-based immunoassay to evaluate T cell-dependent IgG and IgM responses to keyhole limpet hemocyanin (KLH) administration in the juvenile New Zealand white rabbit

ACT 2024 -- The T cell-dependent antibody response (TDAR) assay is an in vivo functional assay capable of characterizing the immune response to an immunogen. It is used for safety assessments, in conjunction with other toxicologic endpoints, to evaluate test article-induced immune modulation. The TDAR assay is a critical component in preclinical safety assessments of large-molecule biologics and routinely performed in rodents, dogs and nonhuman primates. In this method development study, we seek to establish a TDAR assay in juvenile rabbits. Rabbits were chosen for this study because they are sensitive to a number of agents known to cause reproductive or developmental toxicity. Rabbits historically have been used as the second species in safety evaluation studies of this type (evaluating potentially teratogenic agents) and are recommended by appropriate regulatory agencies. The New Zealand white rabbit was selected based on availability of historical control data and susceptibility to known developmental toxicants.

The power of movement: How physical activity can reduce the risk of breast cancer

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer related deaths among women in the United States. The steady increase in the number of patients diagnosed with breast cancer has been attributed to lifestyle changes that have taken place since the 1980s, including increased use of alcohol and tobacco, high-fat and high-sugar diets, women opting to not have children or to delay pregnancy, and low levels of physical activity. Regular physical activity and maintaining a healthy weight have been associated with a lower risk of developing multiple chronic diseases and 13 different types of cancer, including breast cancer. Studies have shown that women who get regular physical activity have lower risk of developing breast cancer than women who do not exercise. 

Labcorp Launches New Global Trial Connect Enhancements to Streamline Site Workflow

BURLINGTON, N.C. (November 12, 2024) — Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, announced today enhancements to Global Trial Connect, a suite of digital, data and operational solutions available to Labcorp Central Laboratory clients aimed at increasing the speed of clinical trials at the heart of clinical research – investigator sites.  

Labcorp Global Trial Connect Site workflow facilitation

The increased complexity of clinical trials is causing an increased burden on investigator sites leading to less time with their patients. As part of our commitment to streamlining clinical trial operations for both sites and sponsors through our Labcorp Global Trial Connect delivers site workflow facilitation that enables accelerated trial delivery to drive critical therapies to patients in need. Reduce Errors: Fully digital lab requisitions integrated with patient visit workflows. Simplify Sample Collection: Step-by-step guided workflows minimize burdens on sites. Real-time access to sample location: with end-to-end sample oversight.