• Targeting Molecular Mechanism of Vascular Smooth Muscle Senescence Induced by Angiotensin II, A Potential Therapy via Senolytics and Senomorphics

      Cardiovascular Research Center (Temple University) (2020-09-09)
      Cardiovascular disease (CVD) is a prevalent issue in the global aging population. Premature vascular aging such as elevated arterial stiffness appears to be a major risk factor for CVD. Vascular smooth muscle cells (VSMCs) are one of the essential parts of arterial pathology and prone to stress-induced senescence. The pervasiveness of senescent VSMCs in the vasculature increases with age and can be further expedited by various stressing events such as oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, and chronic inflammation. Angiotensin II (AngII) can induce many of these responses in VSMCs and is thus considered a key regulator of VSMC senescence associated with CVD. Understanding the precise mechanisms and consequences of senescent cell accumulation may uncover a new generation of therapies including senolytic and senomorphic compounds against CVD. Accordingly, in this review article, we discuss potential molecular mechanisms of VSMC senescence such as those induced by AngII and the therapeutic manipulations of senescence to control age-related CVD and associated conditions such as by senolytic.
    • Targeting SARS-CoV-2 M3CLpro by HCV NS3/4a Inhibitors: In Silico Modeling and In Vitro Screening

      Institute of Computational Molecular Science (Temple University) (2021-02-04)
      Currently the entire human population is in the midst of a global pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2). This highly pathogenic virus has to date caused >71 million infections and >1.6 million deaths in >180 countries. Several vaccines and drugs are being studied as possible treatments or prophylactics of this viral infection. M3CLpro (coronavirus main cysteine protease) is a promising drug target as it has a significant role in viral replication. Here we use the X-ray crystal structure of M3CLpro in complex with boceprevir to study the dynamic changes of the protease upon ligand binding. The binding free energy was calculated for water molecules at different locations of the binding site, and molecular dynamics (MD) simulations were carried out for the M3CLpro/boceprevir complex, to thoroughly understand the chemical environment of the binding site. Several HCV NS3/4a protease inhibitors were tested in vitro against M3CLpro. Specifically, asunaprevir, narlaprevir, paritaprevir, simeprevir, and telaprevir all showed inhibitory effects on M3CLpro. Molecular docking and MD simulations were then performed to investigate the effects of these ligands on M3CLpro and to provide insights into the chemical environment of the ligand binding site. Our findings and observations are offered to help guide the design of possible potent protease inhibitors and aid in coping with the COVID-19 pandemic.
    • Telehealth in school-based practice: Perceived viability to bridge global OT practitioner shortages prior to COVID-19 global health emergency

      Abbott-Gaffney, Cynthia; Jacobs, Karen (2020-10-20)
      BACKGROUND: Prior to the COVID-19 global health emergency, telehealth was an emerging occupational therapy (OT) service delivery model possessing many positive attributes. These include the potential to offset well-documented global occupational therapy practitioner (OTP) shortages. However, wide-spread adoption of telehealth as a delivery model in school-based practice is lacking in the OT evidence literature. While the COVID-19 global health emergency propelled many OTPs into the use of telehealth technologies, in some cases with minimal preparation, an investigation was conducted into the likelihood of telehealth adoption when comprehensive training was provided so that appropriateness of student fit for telehealth could be determined and essential planning could take place. OBJECTIVE: Prior to the COVID-19 global health emergency, a comprehensive training program was developed incorporating detailed perceptions of OTPs experienced in and new to telehealth in school-based practice as measured via surveys with the goal of increasing adoption of telehealth technologies for the delivery of OT services. Following the completion of the online New to Telehealth Pre-training Survey, OTPs new to telehealth were invited to complete the OT Telehealth Primer: School-based Practice training program. Analysis of pre- and post-training surveys yielded information about attitudinal changes experienced post-training. METHODS: Prior to the COVID-19 global health emergency, school-based occupational therapy practitioners (OTP) experienced in telehealth were invited to complete a survey exploring benefits and barriers encountered in the delivery of OT services using telehealth. OTPs new-to-telehealth were invited to complete a different survey intended to explore attitudes about the potential use of telehealth. Data collected from both surveys were used to develop a comprehensive training program, The OT Telehealth Primer for School-based Practice. OTPs new-to-telehealth were invited to complete the training program and a post-training survey. A descriptive data analysis was completed on responses from pre- to post-training surveys and the chi-square test of independence was used to evaluate difference in reported likelihood of adopting telehealth into practice before and after training. RESULTS: Prior to the COVID-19 global health emergency, the top benefits identified by the OTP Experienced Telehealth-User Survey included: 1) service access, 2) collaboration and carry-over with team members, 3) efficiency themes, and 4) student engagement and comfort. Top benefits identified by the OTP New to Telehealth Survey identified the same top benefits after participating in the training program. A significant decrease in perceived barriers was noted in scores from pre- to post-training by OTPs new to telehealth. The perceived barriers that did not significantly decrease post-training suggest the need for future education and future protocol development. These included: unreliable internet, lack of hands-on opportunity and e-helpers’ (parent, caregiver or support system available to assist the student in person during a telehealth session) decreased comfort with technology. Of the participants who completed the OT Telehealth Primer: School-based Practice, 80% reported being likely to add telehealth as a delivery model for future OT practice. CONCLUSIONS: Prior to the COVID-19 global health emergency, completion of the comprehensive training program OT Telehealth Primer: School-based Practice program yielded improved perceived benefits and an increased likelihood of telehealth adoption into practice by OTPs. However, both OTPs and school administrators require ongoing education for successful widespread adoption to be achieved thus offsetting the global shortage of OTPs and increasing service access. Future research, particularly related to available training and support for the rapid adoption of telehealth technologies during the COVID-19 global health emergency, will yield helpful information about the likelihood of continued use of telehealth in practice.
    • Temple University’s ITA Placement Test in Times of COVID-19

      Center for American Language and Culture (Temple University) (2020-12-24)
      When the COVID-19 pandemic made it impossible to do in-person, on campus testing, we were forced to create a new system to screen International Teaching Assistants (ITA) for Temple university. We used this opportunity to address many of the concerns and problems that we had identified with the previous test, and created a new test that could be administered virtually. The new test (the TU ITA Test) makes it possible to test potential ITAs at any time, allowing departments to make instructor placement decisions far in advance. The TU ITA Test also seems to better assess ITAs’ interactional competence than the previous test, suggesting it might be a more valid ITA screening measure.
    • The Convergence of the COVID-19 and Opioid Health Crises in the US

      Public Policy Lab (Temple University) (Temple University. Public Policy Lab, 2020-08-18)
    • The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

      NGS-SA; COVID-19 Genomics UK (COG-UK) (2021-07-25)
      The emergence and rapid rise in prevalence of three independent SARS-CoV-2 “501Y lineages’’, B.1.1.7, B.1.351 and P.1, in the last three months of 2020 prompted renewed concerns about the evolutionary capacity of SARS-CoV-2 to adapt to both rising population immunity, and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence, all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on various SARS-CoV-2 genes and gene segments (such as S, nsp2 and nsp6), that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.
    • The Hardest Hit: Post-COVID Unemployment in Immigrant-Dense Industries

      Public Policy Lab (Temple University) (Temple University. Public Policy Lab, 2020-08-18)
    • The impact of coronavirus disease 2019 (COVID-19) on older adults with an intellectual disability during the first wave of the pandemic in Ireland

      McCarron, Mary; McCausland, Darren; Luus, Retha; Allen, Andrew; Sheerin, Fintan; Burke, Eilish; McGlinchey, Eimear; Flannery, Fidelma; McCallion, Philip; McCallion|0000-0001-5129-6399 (2021-08-19)
      Background: People with intellectual disability have increased risk of exposure to and adverse outcomes from coronavirus disease 2019 (COVID-19).They also face challenges to mental health and well-being from COVID-19-related social restrictions and service closures. Methods: Data from a supplemental COVID-19 survey from the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) (n=710) was used to assess outcomes from the first infection wave of COVID-19 among adults with intellectual disability aged 40+ years in Ireland. Data was gathered on testing, for symptoms and outcomes; procedures to manage COVID-19; and both stress/anxiety and positive experiences during the pandemic. Demographic and health-related data from the main IDS-TILDA dataset was included in analyses. Results: High rates were identified of health conditions associated with poorer COVID-19 outcomes, including overweight/obesity (66.6%, n=365), high cholesterol (38.6%, n=274) and cardiovascular disease (33.7%, n=239). Over half (53.5%, n=380) reported emotional, nervous or psychiatric disorders. Almost two-thirds (62.4%, n=443) were tested for COVID-19, with 10% (n=71) reporting symptoms and 2.5% (n=11) testing positive. There were no instances of COVID-19 related mortality. Common symptoms included fatigue, fever, and cough. Some participants (7.8%, n=55) moved from their usual home to isolate, most often (n=31) or relocate to a family home (n=11). Three-quarters (78.7%) of those who were symptomatic or who tested positive had plans to manage self-isolation and two-thirds were able to comply with guidelines. Over half (55%, n=383) reported some COVID-19 related stress/anxiety; and a similar proportion reported positive aspects during this period (58%, n=381). Conclusions: Our data suggests that people with intellectual disability avoided the worst impacts of COVID-19 during the first infection wave in Ireland. Nevertheless, participants’ health profiles suggest that this population remains at high risk for adverse infection outcomes. Repeated measures are needed to track health and well-being outcomes across multiple infection waves.
    • The impact of COVID-19 on people ageing with an intellectual disability in Ireland: Protocol for a follow-up survey

      McCarron, Mary; Allen, Andrew; McCausland, Darren; Haigh, Margaret; Luus, Retha; Bavussantakath, Fathima Rosmin; Sheerin, Fintan; Mulryan, Niamh; Burke, Eilish; McGlinchey, Eimear; Flannery, Fidelma; McCallion, Philip; McCallion|0000-0001-5129-6399 (2021-08-23)
      Background: The COVID-19 pandemic and associated lockdowns have had a dramatic impact on many people, but individuals with an intellectual disability, given the prevalence of congregate living and high levels of co-morbid conditions, may be particularly vulnerable at this time. A prior initial survey of participants of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) found that, despite a majority of participants being tested, only a small proportion had tested positive for COVID-19. Furthermore, despite some reporting positive aspects to the lockdown, a similar proportion were experiencing stress or anxiety during the pandemic. The pandemic and lockdowns have continued, and it is possible that experiences and consequences have changed over time. Aim: To explore over time and in greater depth the impact of COVID-19 and associated lockdowns and to further establish rates of infection, rates of vaccination and participants’ experiences. Methods: A structured questionnaire for people with intellectual disability participating in the IDS-TILDA longitudinal study, to be administered by telephone/video in summer 2021. Where participants are unable to respond independently, a proxy respondent will be invited to either assist the participant or answer questions on their behalf. This questionnaire will include questions from the first COVID-19 questionnaire, with extra questions assessing “long COVID” (i.e. COVID-19 lasting for 12 weeks or longer), infection control behaviours, changes in mental health, social contacts and loneliness, frailty, healthcare, and incidence of vaccination. Impact: The results of this survey will be used to inform healthcare provision for people with intellectual disability during the latter stages of the lockdown and into the future.
    • The impact of physical activity on psychological health during Covid-19 pandemic in Italy

      Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-06-24)
      The worldwide spread of COVID-19 has upset the normality of Italian daily life, forcing population to social distancing and self-isolation. Since the containment precautions also concern sport-related activities, home workout remained the only possibility to play sports and stay active during the pandemic. The present study aimed to examine changes in the physical activity levels during self-quarantine in Italy, and the impact of exercise on psychological health. A total of 2974 Italian subjects has completed an online survey, but only 2524 subjects resulted eligible for this study. The questionnaire measured the total weekly physical activity energy expenditure before and during quarantine (i.e. the sum of walking, moderate-intensity physical activities, and vigorous-intensity physical activities) in Metabolic Equivalent Task minutes per week (MET–min/wk) using an adapted version of International Physical Activity Questionnaire and their psychological well-being using the Psychological General Well Being Index. Of the 2524 Italian subjects included in the study, 1426 were females (56.4%) and 1098 males (43.6%). Total physical activity significantly decreased between before and during COVID-19 pandemic (Mean: 2429 vs. 1577 MET–min/wk, ∗∗∗∗p < 0.0001), in all age groups and especially in men (Female, mean: 1994 vs. 1443 MET–min/wk, ∗∗∗∗p < 0.0001; Male, mean: 2998 vs. 1754 MET–min/wk, ∗∗∗∗p < 0.0001). Furthermore, a significant positive correlation was found between the variation of physical activity and mental well-being (r = 0.07541, ∗∗∗p = 0.0002), suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population. Based on this scientific evidence, maintaining a regular exercise routine is a key strategy for physical and mental health during a forced rest period like the current coronavirus emergency.
    • The influence of empowered work environments on the psychological experiences of nursing assistants during COVID-19: a qualitative study

      Travers, Jasmine; Schroeder, Krista; Norful, Allison A.; Aliyu, Sainfer; 0000-0002-2034-7525 (2020-10-16)
      Background: Nursing Assistants (NA) who feel empowered tend to perform their duties better, have higher morale and job satisfaction, and are less likely to leave their jobs. Organizational empowerment practices in hospitals likely shape the psychological experiences of empowerment among these personnel; however, little is known about this relationship. Objective: We used qualitative inquiry to explore the relationship between organizational empowerment structural components and feelings of psychological empowerment among hospital frontline workers during a public health emergency. Methods: Kanter’s Theory of Structural Empowerment and Spreitzer’s Psychological Empowerment in the Workplace Framework were applied to identify the conceptual influences of organizational practices on psychological experiences of empowerment. In-depth interviews were conducted with a convenience sample of NAs, caring for hospitalized COVID-19 patients. Directed content analysis was performed to generate a data matrix consisting of the psychological experiences of meaning, competence, self-determination, and impact embedded under the organizational structural components of information, resources, support, and opportunity. Results: Thirteen NAs (mean age = 42 years, 92% female) completed interviews. Information, or lack thereof, provided to the NAs influenced feelings of fear, preparation, and autonomy. Resources (e.g., protocols, equipment, and person-power) made it easier to cope with overwhelming emotions, affected the NAs’ abilities to do their jobs, and when limited, drove NAs to take on new roles. NAs noted that support was mostly provided by nurses and made the NAs feel appreciated, desiring to contribute more. While NAs felt they could consult leadership when needed, several felt leadership showed little appreciation for their roles and contributions. Similar to support, the opportunity to take care of COVID-19 patients yielded a diverse array of emotions, exposed advances and gaps in NA preparation, and challenged NAs to autonomously develop new care practices and processes. Conclusion: Management and empowerment of healthcare workers are critical to hospital performance and success. We found many ways in which the NAs’ psychological experiences of empowerment were shaped by the healthcare system’s empowerment-related structural conditions during a public health emergency. To further develop an empowered and committed critical workforce, hospitals must acknowledge the organizational practice influence on the psychological experiences of empowerment among NAs.
    • The Legal Response to COVID-19: Legal Pathways to a More Effective and Equitable Response

      Center for Public Health Law Research (Temple University) (2021-01)
    • The Lived Experience of Being Diagnosed With COVID-19 Among Black Patients: A Qualitative Study

      Aliyu, Sainfer; Travers, Jasmine L.; Norful, Allison A.; Clarke, Michael; Schroeder, Krista; Schroeder|0000-0002-2034-7525 (2021-03-18)
      Diagnosis and hospitalization for COVID-19 are disproportionately higher among black persons. The purpose of this study was to explore the lived experience of being diagnosed with COVID-19 among black patients. Semistructured one-on-one interviews with black patients diagnosed with COVID-19 were conducted. Data were analyzed using conventional content analysis and a directed content approach. Fifteen patients participated and 3 themes were identified: Panic amidst a COVID-19 diagnosis, Feeling the repercussion of the diagnosis, and Personal assessment of risks within one’s individual environment. Fear of dying, inadequate health benefits, financial issues, and worries about spreading the virus to loved ones were acknowledged by the patients as critical areas of concerns. Majority of the patients looked to God as the ultimate way of surviving COVID-19. However, none of the patients reported receiving support for spiritual needs from health care providers. This is the first study to investigate the lived experience of being diagnosed with COVID-19 among black patients. Our results highlight several factors that put this group at increased risk for COVID-19 and where additional strategies are needed to address these inadequacies. Integrating public health interventions to reduce socioeconomic barriers and integrating spirituality into clinical care could improve patient care delivery.
    • The Post-Lockdown Era: What Is Next in Italy?

      Pomara, Cristoforo; Li Volti, Giovanni; Cappello, Francesco; 0000-0001-9288-1148 (2020-07-15)
    • The role of epidemiologists in SARS-CoV-2 and COVID-19 research

      International Network for Epidemiology in Policy COVID-19 Group (2020-10-17)
    • The Role of Social Reward and Corticostriatal Connectivity in Substance Use

      Sazhin, Daniel; Frazier, Angelique M.; Haynes, Caleb R.; Johnston, Camille R.; Chat, Iris Ka-Yi; Dennison, Jeffrey B.; Bart, Corinne P.; McCloskey, Michael E.; Chein, Jason M.; Fareri, Dominic S.; Alloy, Lauren B.; Jarcho, Johanna M.; Smith, David V. (2020-10-29)
      This report describes an ongoing R03 grant that explores the links between trait reward sensitivity, substance use, and neural responses to social and nonsocial reward. Although previous research has shown that trait reward sensitivity and neural responses to reward are linked to substance use, whether this relationship is impacted by how people process social stimuli remains unclear. We are investigating these questions via a neuroimaging study with college-aged participants, using individual difference measures that examine the relation between substance use, social context, and trait reward sensitivity with tasks that measure reward anticipation, strategic behavior, social reward consumption, and the influence of social context on reward processing. We predict that substance use will be tied to distinct patterns of striatal dysfunction. Specifically, reward hyposensitive individuals will exhibit blunted striatal responses to social and non-social reward and enhanced connectivity with the orbitofrontal cortex; in contrast, reward hypersensitive individuals will exhibit enhanced striatal responses to social and non-social reward and blunted connectivity with the orbitofrontal cortex. We also will examine the relation between self-reported reward sensitivity, substance use, and striatal responses to social reward and social context. We predict that individuals reporting the highest levels of substance use will show exaggerated striatal responses to social reward and social context, independent of self-reported reward sensitivity. Examining corticostriatal responses to reward processing will help characterize the relation between reward sensitivity, social context and substance use while providing a foundation for understanding risk factors and isolating neurocognitive mechanisms that may be targeted to increase the efficacy of interventions.
    • The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in vitro models of the human blood–brain barrier

      Center for Substance Abuse Research (Temple University) (2020-10-11)
      As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor binding domain (RBD) and the S2 subunit. First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex. Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions. Analysis of cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48 h exposure window. Introduction of spike proteins to in vitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties. Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface. Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.
    • The Use of Tissue Engineering to Fabricate Perfusable 3D Brain Microvessels in vitro

      Udeni Galpayage Dona, Kalpani N.; Hale, Jonathan Franklin; Salako, Tobi; Anandanatarajan, Akanksha; Tran, Kiet A.; De Ore, Brandon J.; Galie, Peter Adam; Ramirez, Servio Heybert; Andrews, Allison Michelle (2021-08-31)
      Tissue engineering of the blood-brain barrier (BBB) in vitro has been rapidly expanding to address the challenges of mimicking the native structure and function of the BBB. Most of these models utilize 2D conventional microfluidic techniques. However, 3D microvascular models offer the potential to more closely recapitulate the cytoarchitecture and multicellular arrangement of in vivo microvasculature, and also can recreate branching and network topologies of the vascular bed. In this perspective, we discuss current 3D brain microvessel modeling techniques including templating, printing, and self-assembling capillary networks. Furthermore, we address the use of biological matrices and fluid dynamics. Finally, key challenges are identified along with future directions that will improve development of next generation of brain microvasculature models.
    • The Utility of Anti-Covid-19 Desks in Italy, Doubts and Criticism

      Bergamin, Marco; Musumeci, Giuseppe; Musumeci|0000-0002-8260-8890 (2020-12-30)
    • Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia

      Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2021-02-17)
      Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients. Methods: UMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal tissue microarrays (TMAs), and by flow cytometry on healthy peripheral blood/bone marrow-derived cells, on 10 different T-ALL cell lines, and on 110 T-ALL primary patient-derived cells. CD43-UMG1 binding site was defined through a peptide microarray scanning. ahuUMG1 was generated by Genetic Glyco-Engineering technology from a novel humanized mAb directed against UMG1 (huUMG1). BTCEs were generated as IgG1-(scFv)2 constructs with bivalent (2+2) or monovalent (2+1) CD3ε arms. Antibody dependent cellular cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP) and redirected T-cell cytotoxicity assays were analysed by flow cytometry. In vivo antitumor activity of ahUMG1 and UMG1-BTCEs was investigated in NSG mice against subcutaneous and orthotopic xenografts of human T-ALL. Results: Among 110 T-ALL patient-derived samples, 53 (48.1%) stained positive (24% of TI/TII, 82% of TIII and 42.8% of TIV). Importantly, no expression of UMG1-epitope was found in normal tissues/cells, excluding cortical thymocytes and a minority (<5%) of peripheral blood T lymphocytes. ahUMG1 induced strong ADCC and ADCP on T-ALL cells in vitro, which translated in antitumor activity in vivo and significantly extended survival of treated mice. Both UMG1-BTCEs demonstrated highly effective killing activity against T-ALL cells in vitro. We demonstrated that this effect was specifically exerted by engaged activated T cells. Moreover, UMG1-BTCEs effectively antagonized tumor growth at concentrations >2 log lower as compared with ahuUMG1, with significant mice survival advantage in different T-ALL models in vivo. Conclusion: Altogether our findings, including the safe UMG1-epitope expression profile, provide a framework for the clinical development of these innovative immune-therapeutics for this still orphan disease.