Expansion and Characterization of Human Melanoma Tumor-Infiltrating Lymphocytes (TILs)

Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Writing in English as an Additional Language at Key Stage 2

[Published without an abstract]. Introduction: Researchers from the University of Leeds were commissioned by the Department for Education and Skills (DfES) to conduct research into the writing of pupils at Key Stage 2 (KS2) who use English as an additional language (EAL) and who are defined as ‘advanced learners’, in that they have been in the UK for at least five years. Scripts produced by 264 pupils for the 2003 English National Curriculum Test (Writing) were analysed qualitatively and quantitatively to identify features of writing that pupils learning EAL handle less confidently than their peers who use English as a mother tongue (EMT). This research adds to previous evidence gathered about EAL writing at Key Stage 4 (KS4) in an earlier, Ofstedfunded, project by the same author (Cameron 2003)

International language test taking among young learners : a Hong Kong case study

Many children around the globe are learning English as a foreign language, especially in Asia. Numbers of participants and development of programs are increasing rapidly, as is a commercial testing movement targeted toward assessing this group of young learners. For example, the popular Cambridge Young Learners English test series has had more than 360,000 young testers globally (Cambridge ESOL Examinations, 2004, 2007). Published research on assessment for young learners has focused on developing reliable and appropriate assessment instruments at school or national levels, but little work has focused on the private uses of commercial international language tests for children. Reporting on a 3-year project investigating Hong Kong young learners' participation in commercial international language test taking and preparation, this article explores stakeholders' perceptions on the practice in order to examine the social consequences. The project adopted a multimethod qualitative approach with data including interviews with stakeholders from the education and commercial sectors, classroom observations, participant observation in online parenting forums, and documentary research on media coverage and advertisements. Our findings suggested that in lieu of clear and perceived fairness in their own education system, stakeholders were using language tests as a grassroots movement to gain access to material educational resources.19 page(s

Narratives of second language identity amongst young English learners in Hong Kong

This article reports on an exploratory study responding to the problem of understanding how young learners position themselves as speakers of a foreign language. A group of 24 Hong Kong primary-school children (ages 10-12) who are in the process of simultaneously learning English and developing narratives of identities as English speakers, participated in a photo-elicitation project. Two distinct narratives of identity were found. 'Cosmopolitans' seemed to draw on multiple resources, largely based on their access to the social and economic benefits of using a great variety of English learning opportunities and popular culture media. 'Pragmatists' had fewer resources and were more uncertain about their future learning opportunities. This study demonstrates the importance of considering how educational policy, cultural values, and distribution of resources may impact on young learners studying in similar contexts. Implications are explored and suggestions made for ways teachers can support and foster identity development.11 page(s

Ethics, Technology and the Challenges of Documenting History in Real Time

New technologies including mobile phones and use of social media software have made available a plethora of new sources for news and information that both complement and contrast with traditional news sources. This content is relevant to research libraries and archives around the world. Yet most of it does not get deposited into library and archival collections in traditional ways. Libraries and archives need to be innovative and proactive about seeking it out from numerous participants and scraping it off social network sites in real time to insure authenticity and reliability. At UCLA and NYU we have been collecting both digital and physical materials from the front lines of conflict and war-ravaged areas of the world. We've partnered with political activists to develop unique assemblages of ephemera collected on the front lines of social media revolutions. This paper will present two case studies that illustrate the challenges and opportunities for collaboration and community engagement and utilizing new technologies including social media to capture and preserve history in real time

Selection of Shared and Neoantigen-Reactive T Cells for Adoptive Cell Therapy Based on CD137 Separation

Adoptive cell therapy (ACT) of autologous tumor infiltrating lymphocytes (TIL) is an effective immunotherapy for patients with solid tumors, yielding objective response rates of around 40% in refractory patients with metastatic melanoma. Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue for ex vivo expansion and infusion. Only a minor fraction of the administered T cells recognizes tumor antigens, such as shared and mutation-derived neoantigens, and consequently eliminates the tumor. Thus, there are many ongoing effects to identify and select tumor-specific TIL for therapy; however, those approaches are very costly and require months, which is unreasonable for most metastatic patients. CD137 (4-1BB) has been identified as a co-stimulatory marker, which is induced upon the specific interaction of T cells with their target cell. Therefore, CD137 can be a useful biomarker and an important tool for the selection of tumor-reactive T cells. Here, we developed and validated a simple and time efficient method for the selection of CD137-expressing T cells for therapy based on magnetic bead separation. CD137 selection was performed with clinical grade compliant reagents, and TIL were expanded in a large-scale manner to meet cell numbers required for the patient setting in a GMP facility. For the first time, the methodology was designed to comply with both clinical needs and limitations, and its feasibility was assessed. CD137-selected TIL demonstrated significantly increased antitumor reactivity and were enriched for T cells recognizing neoantigens as well as shared tumor antigens. CD137-based selection enabled the enrichment of tumor-reactive T cells without the necessity of knowing the epitope specificity or the antigen type. The direct implementation of the CD137 separation method to the cell production of TIL may provide a simple way to improve the clinical efficiency of TIL ACT