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Itís all in the delivery
In vaccination, a certain subpopulation of dendritic cells is vital to triggering the body’s adaptive immune system, report researchers at The Jackson Laboratory (JAX), Yale University and the IMED Biotech Unit at AstraZeneca. This finding could have major implications for vaccine delivery because, they say, the usual method—intramuscular injection—is likely not the most effective way to target those dendritic cells.
In a paper published in Science Immunology, the team—led by senior co-authors Adam Williams, a JAX assistant professor, and Dr. Stephanie Eisenbarth of Yale—showed that dendritic cells known as cDC2s (for CD11b+ migratory type 2 conventional DCs) are both necessary and sufficient for robust Tfh cell induction. Working with mice that lack a protein needed for cDC2 mobility, the team demonstrated that Tfh cells were not induced and antibodies not produced following vaccination, even in the presence of other, functional dendritic cells.
The authors used inhalants for their research and show that multiple types of DCs access antigens through this delivery form. In particular, cDC2s deliver inhaled antigens to lung-draining lymph nodes, and there induce a potent Tfh response.
In contrast, the usual method of vaccination through intramuscular injection delivers antigen to where cDC2s are relatively scarce. Based on older epidemiological data and a similar repertoire of cDC2s in the superficial layer of the skin, the researchers speculate that intradermal injections may be far more efficient in driving antibody production.
Moreover, more efficient delivery of vaccines could mean that smaller doses could be administered, expanding the number of people who could be vaccinated during a pandemic or when a given vaccine is in short supply.
Williams notes that the work also underscored the importance of using an animal model system rather than in-vitro cell lines. “Not only are dendritic cell types concentrated in different areas of the body, they also migrate to specialized areas within the lymph node. This fundamental aspect of immune architecture is lost in vitro,” says Williams. “Having mouse models in which specific dendritic cells were disabled or deleted was essential for this work.”
While this news is more research-oriented than we usually cover in this section of the magazine, read on for some recent news of more business-focused news in the realm of delivering therapeutic agents.
Medherant signs deal with Japanese transdermal patch company
COVENTRY, U.K.—Medherant, a leader in next-generation transdermal drug delivery, has signed an agreement with a Japanese transdermal patch company, one of the world’s largest patch developers and manufacturers, to evaluate the potential of its TEPI Patch technology to deliver a drug provided by the company.
Medherant will apply its proprietary high-throughput system for skin permeation studies to rapidly evaluate a range of potential formulations of the drug provided by the company. A successful outcome could lead to the company licensing the TEPI Patch technology to develop a product for a market where sales are currently more than $1 billion and patient numbers are rising. The delivery of the drug via a patch is technically challenging, Medherant notes, but the company believes its technology will provide the solution that the unnamed partner company needs.
FDA approves QVAR RediHaler
JERUSALEM—Teva Pharmaceutical Industries Ltd. announced earlier this year that the U.S. Food and Drug Administration (FDA) has approved QVAR RediHaler (beclomethasone dipropionate HFA) inhalation aerosol, a breath-actuated inhaler for the maintenance treatment of asthma as a prophylactic therapy in patients 4 years of age and older. QVAR RediHaler is not indicated for the relief of acute bronchospasm. The product is expected to become commercially available in both 40mcg and 80mcg strengths to patients by prescription during the first quarter of 2018.
QVAR RediHaler differs from conventional metered-dose inhalers (MDIs) as it delivers medication via a breath-actuated MDI, eliminating the need for hand-breath coordination during inhalation.
“When working to manage asthma on a daily basis, proper administration of medication is of paramount importance,” said Dr. Warner W. Carr, associate medical director of Southern California Research at Allergy and Asthma Associates of Southern California Medical Group. “However, research has indicated that approximately 76 percent of patients still struggle to use their MDI inhalers correctly, thus placing them at increased risk for asthma exacerbations.”
Conquering challenges of pediatric drug formulation and delivery
SOMERSET, N.J.—The Catalent Applied Drug Delivery Institute—formed by Catalent to serve as a link between industry and academia—announced earlier this year that it had entered into a collaboration with the Department of Pharmacy Practice at Rutgers University to identify and address the specific challenges of pediatric formulation and drug delivery.
This collaboration will allow for research into the development and administration of medicines to children, including the prevalence of extemporaneous compounding of drug products for ease of administration to pediatric patients, and any safety and efficacy consequences. The goal of the collaboration is to identify therapies and diseases for which there is a high need for pediatric-friendly formulations, and to build awareness and advocate for targeted translational research to address the specific needs of this underserved patient group.