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Adoptive transfer of chimeric antigen receptor (CAR) T lymphocytes is a powerful technology that has revolutionized the way we conceive immunotherapy. The impressive clinical results of complete and prolonged response in refractory and relapsed diseases have shifted the landscape of treatment for hematological malignancies, particularly those of lymphoid origin, and opens up new possibilities for the treatment of solid neoplasms. However, the widening use of cell therapy is hampered by the accessibility to viral vectors that are commonly used for T cell transfection. In the era of messenger RNA (mRNA) vaccines and CRISPR/Cas (clustered regularly interspaced short palindromic repeat–CRISPR-associated) precise genome editing, novel and virus-free methods for T cell engineering are emerging as a more versatile, flexible, and sustainable alternative for next-generation CAR T cell manufacturing. Here, we discuss how the use of non-viral vectors can address some of the limitations of the viral methods of gene transfer and allow us to deliver genetic information in a stable, effective and straightforward manner. In particular, we address the main transposon systems such as Sleeping Beauty (SB) and piggyBac (PB), the utilization of mRNA, and innovative approaches of nanotechnology like Lipid-based and Polymer-based DNA nanocarriers and nanovectors. We also describe the most relevant preclinical data that have recently led to the use of non-viral gene therapy in emerging clinical trials, and the related safety and efficacy aspects. We will also provide practical considerations for future trials to enable successful and safe cell therapy with non-viral methods for CAR T cell generation.

The use of instrumental tools for improving both the diagnostic accuracy and the prognostic soundness in patients with disorders of consciousness (DOC) plays an important role. However, the most recent international guidelines on DOC published by the American and the European Academies of Neurology and by the UK Royal College of Physicians contain heterogeneous recommendations on the implementation of these techniques in the clinical routine for both diagnosis and prognosis. With the present work, starting from the comparison of the DOC guidelines’ recommendations, we look for possible explanations behind such discrepancies considering the adopted methodologies and the reference health systems that could have affected the guidelines’ perspectives. We made a provocative argument about the need to find the most appropriate common methodology to retrieve and grade the evidence, increase the meta-analytic studies, and reduce the health policies that influence on the guidelines development that, in turn, should inform the health policies with the strongest scientific evidence.

IntroductionEvidence from contemporary research has highlighted abnormal subjective pre-psychotic experiences as an expression of schizotropic vulnerability, for which trajectories up to First Rank Symptoms have been described. Embodiment is crucial to the conceptualisation of these experiences as the distinctive feature of schizophrenic phenomena. In fact, these are embedded in precise experiential frameworks such as Diminished Self-Affection and Hyperreflexivity, which constitute in nuce the experience of Dis-Embodiment. The latter responds poorly to conventional therapies, thereby affecting considerably the prognosis quoad valetudinem of Schizophrenia.ObjectivesThis study is intended to explore the use of specific psychomotor therapy protocols aimed at fostering Embodiment in patients with Schizophrenia, especially by investigating its efficacy and specificity on self-perceived body disorders, on characteristic motor abnormalities and on psychopathological dimensions.MethodsThe study involves the participation of 20 patients throughout 10 weekly 90-minute meetings of Embodied Psychomotor Therapy (EPT) in groups of approximately 5 participants. Despite being partially inspired by current approaches, EPT is conceived as a specific activity intended for patients with schizophrenia: each meeting combines intersubjective coordination activities (complex motor sequences, harmonious control of voluntary movement and movement in space, body-awareness), intra-subjective coordination (mirroring, demarcation and identification of one’s own boundaries, single-group dynamics), and exercises aimed at developing motor skills (proprioception, balance, posture, rhythm and speed). At the beginning of the activity (T0) and after 10 meetings (T1) participants will carry out self-administered and externally administered assessments, for the evaluation of motor (BMS, LOFOPT, BBS, AIMS, SRRS), psychopathological (PANSS, FBF, ABP), social functioning (SOFAS) and daily physical activity level (IPAQ) dimensions.ResultsThe study is still ongoing, due to limitations dictated by the Sars-CoV-2 pandemic. Preliminary results at T0 indicate a positive correlation between low levels of daily physical activity (IPAQ) and poor functioning (SOFAS). Significantly higher motor impairment with respect to the general population is also confirmed in all motor scales used. Moreover, a positive correlation between low levels of motor coordination (BMS_MC) and balance (BSS_TOT) was found together with basic symptoms related to loss of control or self-agency (FCQ_KO). Furthermore, the first results suggest an overall improvement in motor performance at T1.ConclusionsThe longitudinal analysis will enable the extent of the impact of EPT on functioning, motor and psychopathological dimensions of the patients to be determined, providing useful elements for planning specific rehabilitation interventions for schizophrenia.Disclosure of InterestNone Declared

IntroductionThe disruption of minimal Self is believed to be a core element of Schizophrenia and intimately connected to a disruption of bodily self, which in turn leads to impairments in intersubjectivity dimension. Motor abnormalities have been associated to Schizophrenia since the early conceptualization of the disorder, as well as inefficient body-related multisensory integration processes are considered nowadays a plausible origin of disembodied Self. In particular, there is evidence for significant abnormalities in Peripersonal Space (PPS) extension in Schizophrenia patients. PPS is the plastic sector of space immediately surrounding our body, whose coherent representation is based on efficient body-related multisensory integration processes. With a specific experimental task based on multisensory integration processing, we estimated PPS size and PPS boundary’s demarcation in 27 Schizophrenia patients, confirming a narrower PPS size and weaker bodily boundary in patients, thus paving the way for a deeper investigation of the mechanisms underlying the disruption of bodily self (Ferroni et al., Schziophr.Bull.2022, 5 1085-1093). We suggest that disembodiment might be responsible for the loss of the immediate linkage between Self and others (“intercorporeality”), so linking the disruption of the corporeal dimension to specific anomalies of intersubjectivity in Schizophrenia patients. Since language is one of the most important instrument through which intersubjectivity unfolds, it is intriguing to hypothesize a connection between language and multi-sensory processing.ObjectivesTherefore, the present study was aimed at investigating possible correlations between patients’ motor impairments in multi-sensory integration processes and their alterations in language and communicative interactions.MethodsTwenty-five outpatients were recruited in an experimental task investigating PPS extension; they were administered the Scale for the Assessment of Thought, Language and Communication (TLC) and the Clinical Language Disorder Rating Scale (CLANG).ResultsOur data showed significant correlations between TLC and CLANG total scores and PPS size, with narrower PPS size for more severe formal thought disorders and higher language and communication impairments.ConclusionsOur preliminary results seem to confirm the presence of a link between language impairment and multi-sensory processing, suggesting that bodily and linguistic disorganization may have a common origin which has yet to be explored in depth. Future research is needed to identify linguistic and motor endophenotypic patterns, potentially intertwined with each other, capable of early predicting Schizophrenia development and thus usable as early diagnostic tools.Disclosure of InterestNone Declared

IntroductionPatients with schizophrenia present severe communication difficulties in various linguistic areas. In the last two decades research has invested significant effort in trying to better characterize the linguistic profile of patients with schizophrenia, with the purpose to help and guide diagnosis and treatment. Moreover, speech data could be easily gathered through non-invasive techniques and are therefore seen as particularly promising by clinicians. However, surprisingly very little is known about interactional dialogue management, i.e. turn-taking, in these patients. ‘Schizophrenic autism’, the peculiar intersubjective experience also linked to anomalies in the sense of the self (‘Self-disorders’) presented by these patients, could be at the basis of an unusual turn-taking management.ObjectivesThe objective of the present study was to investigate turn-taking patterns of patients with schizophrenia and to explore their possible associations with psychopathological dimensions and subjective experiences.MethodsWe obtained double-channel audio-recordings from interviews with twenty patients with schizophrenia (SCZ) and twenty healthy controls (HC). Participants answered general questions to elicit spontaneous dialogues, to improve the ecological validity of the task. The audio files obtained were then analyzed with Praat, a software widely used in experimental phonetics. We subsequently quantified a set of conversational metrics (participant floor occupation, mutual silence, overlap between speakers, speaking turn and pause duration). Patients also underwent a thorough psychopathological and phenomenological evaluation with the Positive And Negative Syndrome Scale (PANSS), the Examination of Anomalous Self Experience scale (EASE) and the Autism Rating Scale (ARS).ResultsOur results show that the SCZ group displayed a reduced participant floor occupation, an increased mutual silence, and shorter speaking turns as compared to the HC. (Fig. 1, Fig. 2). We found significant associations between conversational features and psychopathology (Fig. 3). Two multivariate linear regressions showed that the participant occupation floor and the average speaking turn duration (dependent variables) were negatively related to the severity of negative symptoms and Self-Disorders. Interestingly, Self-Disorders were the best predictors of conversational engagement.Image:Image 2:Image 3:ConclusionsOur results, although preliminary, suggest the existence of peculiar turn-taking patterns in schizophrenia, linked to negative symptoms and disturbances of the subjective experience, particularly in the Self domain. Our results suggest also how the use of experimental linguistic methodology is applicable to clinical settings and underscores the importance of research projects in this field that are strongly interdisciplinary in both design and conduct.Disclosure of InterestNone Declared

IntroductionIn schizophrenia, there is evidence for anomalies in the extension and plasticity of the peripersonal space (PPS), the portion of space surrounding our body, plastically shaped through motor experiences. An impaired multisensory integration at the PPS level would underpin the disembodiment, a core feature of the disorder linked to subjective perturbations of the sense of self (“Self-disorders”) and of the intersubjective dimension (“schizophrenic autism”).ObjectivesThe present study was aimed at: 1) exploring possible associations between PPS data, psychopathological dimensions, and subjective experiences in schizophrenia; 2) identifying a specific PPS profile in patients with early-onset schizophrenia.MethodsA motor training with a tool was used to assess the PPS size and boundaries demarcation in twenty-seven schizophrenia outpatients. Moreover, they underwent a thorough psychopathological evaluation with the Positive And Negative Syndrome Scale (PANSS), the Examination of Anomalous Self Experience scale (EASE) and the Autism Rating Scale (ARS). Subsequently, the sample was divided into early (EOS) and adult-onset (AOS) subgroups, that were compared with respect to their PPS and psychopathological profiles.ResultsPPS features (size and boundaries demarcation) were associated with PANSS negative score, subjective experiences of existential reorientation (EASE Domain 5 scores) and traits of schizophrenic autism (ARS scores; Fig. 1). PPS parameters (Fig. 2) and ARS scores, but not PANSS and EASE differentiated between early and adult-onset subgroups.Image:Image 2:ConclusionsOur results suggest a link between PPS patterns, negative symptoms, and disturbances of the subjective experience, particularly in the intersubjective domain, in schizophrenia. Moreover, they candidate specific PPS profiles and schizophrenic autism traits as EOS markers.Disclosure of InterestNone Declared

IntroductionLanguage and conversation are deeply interrelated: language is acquired, structured, practiced in social interactions and linguistic resources (specifically syntactic, prosodic and pragmatic aspects) contribute to finely tuning turn-taking. Nevertheless, most studies focused on verbal aspects of speech in schizophrenia, with scant attention to their relation to conversation, where language is experienced at most.ObjectivesThe present study was aimed at investigating a possible association between language impairment and conversational characteristics in a sample of clinically stable patients diagnosed with schizophrenia (N = 35, ages 18-65).MethodsA spontaneous speech sample was recorded. For the assessment of language skills, the Scale for the Assessment of Thought, Language and Communication (TLC) and the Clinical Language Disorder Rating Scale (CLANG) were used, while conversational variables were extracted with an innovative method of semi-automatic analysis. The possible associations were investigated through the Pearson Correlation.ResultsFigure 1 represents graphically the correlational matrix between conversational variables and linguistic scale scores. In the heatmap, blue means negative and red positive correlations, the stronger the colour, the larger the correlation magnitude. Moreover, the significant associations are indicated with stars.ConclusionsThe results suggest that in schizophrenia spectrum disorders the disturbances of language, at a syntactic, prosodic and pragmatic level, have significant impact on communicative interaction.Thus, conversation analysis might be a promising method to quantify objectively communicative impairment with the benefit of representing an ecological assessment, examining the performance of patients in the real situation of language use, which is social interaction.DisclosureNo significant relationships.

IntroductionA primary disruption of the bodily self is considered a core feature of schizophrenia patients (SCZ). The “disembodied” self would be underpinned by an inefficient body-related multisensory integration mechanism occurring in the Peripersonal Space (PPS). PPS is a plastic sector of space surrounding our body, whose extent is altered in SCZ. Although PPS represents a malleable interface marking the perceptual border between self and others, no study has investigated the potential alteration of its plasticity in SCZ.ObjectivesWe investigated the PPS extension and its plasticity in SCZ and their potential correlations with the clinical scales.MethodsThirty SCZ and thirty healthy controls (HC) underwent a multisensory task to estimate PPS boundary before and after a motor training. Patients were also administered the Positive And Negative Syndrome Scale (PANSS) and the Examination of Anomalous Self-Experience (EASE).ResultsData confirm a narrower PPS extent in SCZ than in HC, whereas no differences in PPS expansion was found in the two groups after the motor training (Figure 1). Positive symptoms were associated directly with PPS extent and inversely with PPS plasticity. No associations were found between PPS and EASE domains. Figure1: Graphical representation of PPS expansion in SCZ and HC. Both panels show individual normalized sigmoid fitsConclusionsThe present study suggests a narrower PPS extent and a preserved PPS plasticity in SCZ with respect to HC. Both PPS extent and plasticity are related to the severity of positive symptoms. These results highlight the potential role of rehabilitation interventions in order to improve patients’ weakened body boundary.DisclosureNo significant relationships.

Chimeric Antigen Receptor (CAR) T-cell therapy has become a new therapeutic reality for refractory and relapsed leukemia patients and is also emerging as a potential therapeutic option in solid tumors. Viral vector-based CAR T-cells initially drove these successful efforts; however, high costs and cumbersome manufacturing processes have limited the widespread clinical implementation of CAR T-cell therapy. Here we will discuss the state of the art of the transposon-based gene transfer and its application in CAR T immunotherapy, specifically focusing on the Sleeping Beauty (SB) transposon system, as a valid cost-effective and safe option as compared to the viral vector-based systems. A general overview of SB transposon system applications will be provided, with an update of major developments, current clinical trials achievements and future perspectives exploiting SB for CAR T-cell engineering. After the first clinical successes achieved in the context of B-cell neoplasms, we are now facing a new era and it is paramount to advance gene transfer technology to fully exploit the potential of CAR T-cells towards next-generation immunotherapy.

Introduction Self Disorders (SDs) are regarded as the subjective phenotype of Schizophrenia vulnerability. The EASE (Examination of Anomalous Self-Experiences) scale is the most detailed and widely used instrument to investigate SDs, but it requires long administration times and specific training. The IPASE (Inventory of Psychotic-like Anomalous Self-Experiences) scale might be a self-administered instrument of widespread use for an easier SDs investigation. Objectives The present study was aimed at validating the Italian version of IPASE, testing its internal consistency and usability for a first level SDs survey. A secondary objective was to confirm the correlations between IPASE, EASE, main symptom dimensions, subjective bodily experiences, symptoms of schizophrenic autism as well as levels of global functioning. Methods Fifty patients with Schizophrenia were administered the IPASE scale in its Italian version, the Examination of Anomalous Self-Experiences scale (EASE), the Positive And Negative Symptoms Scale (PANSS), the Social and Occupational Functioning Assessment Scale (SOFAS) to assess global functioning, the Autism Rating Scale (ARS) and the Abnormal Bodily Phenomena questionnaire (ABPq). The internal consistency of IPASE in its Italian version was investigated and the correlations between IPASE, EASE, ABP, ARS, PANSS and SOFAS were explored. Results The internal consistency of the Italian version of IPASE was high (α 0.97). The IPASE and EASE total scores were positively correlated with each other, as were many of the conceptually related subdomains of both scales. The IPASE score was negatively correlated with global functioning (SOFAS) and positively correlated with total PANSS scores and with PANSS negative domain. Moreover, the IPASE total score was positively correlated with autism dimension (ARS), while anomalies in subjective experience of the lived body were coherently correlated with higher scores in IPASE “somatization” subdomain. Conclusions The IPASE may be an easy instrument with high internal consistency for an initial investigation of SDs. IPASE domains appear to be correlated with the SDs investigated through EASE and with the main symptomatologic dimensions of Schizophrenia, in particular with negative symptoms. IPASE might also be a useful instrument for a first level investigation of subjective experiences concerning intersubjectivity and bodily dimensions. SDs are confirmed to be a core feature of the schizophrenia psychopathology, with a adverse impact on global functioning. Disclosure of Interest None Declared