Contents
19 June 2019
Vol 11, Issue 497
Vol 11, Issue 497
Perspective
- Vaccines and global health: In search of a sustainable model for vaccine development and delivery
Sustainable development of vaccines for global health requires considerable investment and close collaborations between public and private sectors.
Research Articles
- Epigenetic activation and memory at a TGFB2 enhancer in systemic sclerosis
NF-κB and BRD4 epigenetically activate a TGFB2 enhancer to lock sclerotic patient fibroblasts into a profibrotic synthetic state.
- Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics
An in vitro multi-organ system evaluates the efficacy and potential off-target toxicities of anticancer parent drugs and metabolites.
- A Mucin 16 bispecific T cell–engaging antibody for the treatment of ovarian cancer
A CD3 bispecific antibody targeting Mucin 16 shows preclinical efficacy in mouse tumor models and a tolerable safety profile in nonhuman primates.
- Targeting pancreatic islet PTP1B improves islet graft revascularization and transplant outcomes
Inhibition of tyrosine phosphatase PTP1B in mouse and human islets promotes islet revascularization and improves graft survival and function.
- Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma
Frequently observed DNA copy number gains of TCF4 in ABC-like DLBCL promote immunoglobulin expression and are targetable by BET inhibition.
Technical Comment
- Comment on “An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness”
Increased airway hyperresponsiveness and epithelial remodeling in asthmatic LTA4H-KO mice may be mediated by CysLTs rather than elevated tripeptide PGP.
Technical Response
- Response to Comment on “An extracellular matrix fragment drives epithelial remodeling and airway hyperresponsiveness”
We provide further evidence to support our assertion that PGP is a potent regulator of epithelial remodeling.
Editors' Choice
- The right adjuvant gives T follicular helper cells a boost
The vaccine adjuvant GLA-SE increases the magnitude and longevity of antibody responses by increasing the quantity of T follicular helper cells in humans.
- Coaxing cancer control by modulating COX-2
Mouse models of pancreatic ductal adenocarcinoma respond to immunotherapy when given in combination with the cyclooxygenase-2 inhibitor celecoxib.
- Neutralizing antibodies for AAV vectors: The strange case of AAV5
A clinical trial on hemophilia B demonstrated efficient liver targeting with AAV5 in the presence of neutralizing antibodies.
About The Cover
ONLINE COVER Clearing Out the Cobwebs. Systemic sclerosis (SSc) results in the progressive deposition of collagen fibers in the skin and viscera, as shown in this patient skin explant (type 1 collagen, gold; type 3 collagen, green). Shin et al. identified a constitutively activated enhancer in SSc that promoted fibrosis by locking fibroblasts into expressing TGFB2. The enhancer was epigenetically regulated in part by BRD4. A bromodomain inhibitor promoted the clearance of cutaneous collagen in ex vivo patient skin samples. These findings identify a target for developing new therapies to treat fibrosis in patients with SSc. [CREDIT: SHIN ET AL./SCIENCE TRANSLATIONAL MEDICINE]