Trans-Atlantic Engagement: a Novel Dental Educational Exchange

Introduction Newcastle University School of Dental Sciences (NUSDS) and Indiana University School of Dentistry in the United States of America (IUSD) are like-minded institutions committed to civic engagement. Over the last 15 years, both universities have built civic engagement into the dental curricula, however each institution operates within significantly different healthcare systems. Aim Co-development of unique collaborative dental education; the first UK/US educational exchange programme engaged with the dental student community. Design A dental educational exchange was developed enabling NUSDS and IUSD students to learn alongside each other within dental and community settings in both countries. Students participate in a unique face-to-face collaborative and interdisciplinary education programme within respective dental schools and by a series of video conferences scheduled before on-site visits. They gain mutual awareness of delivery, access to care and possible barriers facing patients relating to the oral healthcare systems in England, the state of Indiana and the USA. Logistical considerations were significant, aided by scoping visits to the respective partner school and video conferencing. Planning encompassed timetable restrictions, scheduling student video conferences, students' clinical access/observerships, occupational health clearances, overall educational content, student/staff evaluation and potential areas for education research. Conclusions Currently in its fourth year, this is a unique example of a collaborative educational exchange between the UK and USA

Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors

Background: T cells expressing chimeric antigen receptors (CARs) have shown exciting promise in cancer therapy, particularly in the treatment of B-cell malignancies. However, optimization of CAR-T cell production remains a trial-and-error exercise due to a lack of phenotypic benchmarks that are clearly predictive of anti-tumor functionality. A close examination of the dynamic changes experienced by CAR-T cells upon stimulation can improve understanding of CAR–T-cell biology and identify potential points for optimization in the production of highly functional T cells. Methods: Primary human T cells expressing a second-generation, anti-CD19 CAR were systematically examined for changes in phenotypic and functional responses to antigen exposure over time. Multi-color flow cytometry was performed to quantify dynamic changes in CAR-T cell viability, proliferation, as well as expression of various activation and exhaustion markers in response to varied antigen stimulation conditions. Results: Stimulated CAR-T cells consistently bifurcate into two distinct subpopulations, only one of which (CARhi/CD25+) exhibit anti-tumor functions. The use of central memory T cells as the starting population and the resilience—but not antigen density—of antigen-presenting cells used to expand CAR-T cells were identified as critical parameters that augment the production of functionally superior T cells. We further demonstrate that the CARhi/CD25+ subpopulation upregulates PD-1 but is resistant to PD-L1-induced dysfunction. Conclusions: CAR-T cells expanded ex vivo for adoptive T-cell therapy undergo dynamic phenotypic changes during the expansion process and result in two distinct populations with dramatically different functional capacities. Significant and sustained CD25 and CAR expression upregulation is predictive of robust anti-tumor functionality in antigen-stimulated T cells, despite their correlation with persistent PD-1 upregulation. The functionally superior subpopulation can be selectively augmented by careful calibration of antigen stimulation and the enrichment of central memory T-cell type. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0519-8) contains supplementary material, which is available to authorized users