Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. Twenty-seven out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. Ex vivo cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6 ± 13.44%. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient's cells compared to healthy donor's cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients and largely determined by the initial product. T CM and T EM were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a T N or T CM phenotype, in average, which are the Castella et al. Semi-automated CAR T-Cell Manufacturing subsets capable of establishing a long-lasting T-cell memory in patients. An in-depth analysis to identify individual factors contributing to the optimal T-cell phenotype revealed that ex vivo cell expansion leads to reduced numbers of T N , T SCM , and T EFF cells, while T CM cells increase, both due to cell expansion and CAR-expression. Overall, our results show for the first time that clinical-grade production of CAR T-cells for heavily pre-treated patients using CliniMACS Prodigy system is feasible, and that the obtained products meet the current quality standards of the field. Reduced ex vivo expansion may yield CAR T-cell products with increased persistence in vivo.

Este artículo pretende analizar el carácter intertextual de una obra clásica de la literatura infantil y juvenil como es la novela de Lewis Carroll, Alicia en el país de las maravillas. El trabajo presentado consiste en un primer apartado de introducción sobre las nociones teóricas de hipertextualidad e intertextualidad. Posteriormente, nos adentraremos en el análisis de la novela victoriana como ejemplo de texto hipertextual desde dos vertientes: por un lado el concepto de literatura dentro de la literatura que se da en la novela y por otro lado analizaremos las relaciones intertextuales que se producen entre el texto de Carroll y otras obras literarias y audiovisuales tales como la versión cinematográfica de Tim Burton o la novela de Diego Arboleda, Prohibido leer a Lewis Carroll. Finalmente, valoraremos las relaciones de Alicia con textos hipermodales, que permiten comprender mejor la novela decimonónica y ampliar el horizonte de expectativas del lector.

The new contexts of literary education allow for the creation of digital reading and writing practices related to what specialised literature calls digital literature. Among these practices and with an eminently theoretical content and with an example of this content, in this paper, we want to focus our gaze on cyberpoetry, conceived as an exercise in literary creativity that firstly involves use of technology and specific software for the digital creation of poetic texts and, last but not least, knowledge and mastery of poetic language and the literary conventions linked thereto. From this point of view, in initial teacher training, we work with future teachers to create cyberpoems with a dual purpose: on the one hand, to reflect on what literary reading in digital format entails and to rehearse reading mediation processes that can be carried out with this type of literature, and, on the other, to begin in the digital creation of cyberpoems that, later, may be presented and worked in a real context of the school classroom. In this paper, we present digital practices of literary reading that have been created by student teachers in initial training. The creation of these practices has been carried out with the Genially tool. For data collection, the URL of each creation is accessed in order to analyse them. The analysis of the data follows the parameters of the qualitative methodology, specifically based on three categories of analysis for each digital creation: multimodality, hypertextuality and the interaction of each digital reading proposal. The conclusions of all this allow us to affirm that the creation of cyberpoems is an exercise in literary creativity that has to take into account the digital dimension of the literary text and its reading comprehension in a multimodal environment. Thus, the teacher in initial training carries out a digital literary mediation exercise, of a creative type, which he will later carry out in his pedagogical practice.

Lectura, arte, poesía, metacognición.