Medicine and Health Sciences Commons^™

Myeloid-Derived Suppressor Cell Mitochondrial Fitness Governs Chemotherapeutic Efficacy In Hematologic Malignancies, Saeed Daneshmandi, Jee Eun Choi, Qi Yan, Cameron R. Macdonald, Manu Pandey, Mounika Goruganthu, Nathan Roberts, Prashant K. Singh, Richard M. Higashi, Andrew N. Lane, Teresa W-M Fan, Jianmin Wang, Philip L. Mccarthy, Elizabeth A. Repasky, Hemn Mohammadpour

Markey Cancer Center Faculty Publications

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprogram- ing, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of …

Randomized Controlled Trial Of The Cmr Immersive Virtual Reality (Ivr) Headset Training Compared To E-Learning For Operating Room Configuration Of The Cmr Versius Robot, Catherine L Eley, Varun Palaniappan, Abbie Carter, Opeyemi Sogaolu, James Horwood, Michael Davies, Jared Torkington, James Ansell

Faculty, Staff and Student Publications

Robotic surgery offers potential advantages over laparoscopic procedures, but the training for configuring robotic systems in the operating room remains underexplored. This study seeks to validate immersive virtual reality (IVR) headset training for setting up the CMR Versius in the operating room. This single-blinded randomized control trial randomised medical students with no prior robotic experience using an online randomiser. The intervention group received IVR headset training, and the control group, e-learning modules. Assessors were blinded to participant group. Primary endpoint was overall score (OS): Likert-scale 1-5: 1 reflecting independent performance, with increasing verbal prompts to a maximum score of 5, …

Simultaneous Extraction And Quantitative Analysis Of S-Methyl-L-Cysteine Sulfoxide, Sulforaphane And Glucosinolates In Cruciferous Vegetables By Liquid Chromatography Mass Spectrometry, Armaghan Shafaei, Caroline R. Hill, Jonathan M. Hodgson, Lauren C. Blekkenhorst, Mary C. Boyce

Research outputs 2022 to 2026

Sulfur containing compounds including glucosinolates (GLS), sulforaphane (SFN) and S-methyl-L-cysteine sulfoxide (SMCSO) have been proposed to be partly responsible for the beneficial health effects of cruciferous vegetables. As such, greater understanding of their measurements within foods is important to estimate intake in humans and to inform dietary intervention studies. Herein is described a simple and sensitive method for simultaneous analysis of 20 GLS, SFN and SMCSO by liquid chromatography mass spectrometry. Analytes were effectively retained and resolved on an Xbridge C18 column. Detection can be achieved using high resolution or unit resolution mass spectrometry; the latter making the method more …

The Impact Of The Gut-Brain Axis On Alzheimer’S Disease, Elissa Wakim

Best Integrated Writing

Elissa’s review for the Graduate Biomedical Review focuses on the links between the gastrointestinal tract and the brain; the gut-brain axis and the development of Alzheimer’s disease. As a student in the Microbiology and Immunology Masters Program Elissa was particularly interested in the gut microbiota and their connection to neurodegenerative disease. She tidily reviewed the literature and wrote a fascinating and compelling piece of work.

Best Integrated Writing Spring 2024 - Complete Edition, Wright State University School Of Humanities And Cultural Studies, Kristie Mckiernan, Tracy Smith

Best Integrated Writing

Best Integrated Writing includes excellent student writing from Integrated Writing courses taught at Wright State University. This is the first issue after a 5 year hiatus.

Attitudes And Self-Efficacy Of Swimming Coaches Towards The Inclusion Of Swimmers With Autism Spectrum Disorder, Eleftheria Kasagianni, Dimitrios Kokaridas, Panagiotis Varsamis, Vasilis Tsimaras

International Journal of Aquatic Research and Education

The purpose of this study was to investigate the attitudes and self-efficacy of swimming coaches regarding the inclusion of swimmers with autism spectrum disorder (ASD). The sample consisted of 150 Greek swimming coaches with an average age of 29.58 years. Each participant completed the Swimming Coaches Attitudes towards Inclusion Questionnaire for perceptions assessment and the Biddle and Goudas (1997) self-efficacy questionnaire. The statistical analysis used SPSS 27 to calculate Cronbach’s alpha, Pearson product-moment correlations, independent t-tests, and ANOVA. The findings of the study showed that the swimming coaches expressed positive attitudes and a high percentage of perceived self-efficacy towards the …

In This Issue 14:3, Stephen J. Langendorfer Ph.D.

International Journal of Aquatic Research and Education

In This Issue 14:3

A Research Framework To Improve Evidence-Based Practice Surrounding The Resuscitation Response To Drowning In Surf Lifesaving, Elissa Hooper, Aaron T. Scanlan, Shayne D. Baker, Samantha Fien

International Journal of Aquatic Research and Education

Surf lifesaving members are essential first responders who patrol public waterways, performing rescues and resuscitation to individuals in the community when needed. In this way, surf lifesaving members experience arduous physical requirements alongside extensive psychological stress during resuscitation. Surf Life Saving Queensland (SLSQ) represents the predominant, frontline lifesaving service in Queensland, Australia; however, little research has explored key aspects of drowning resuscitations involving this organisation, as well as in the broader lifesaving industry, limiting our current understanding on this vital topic. We sought to explore key aspects of drowning resuscitations within SLSQ and create a framework to generate evidence-based practice. …

‘You Have To Respect The Water’: Participant Experiences Of Appreciating And Managing The Risks Associated With Open Water Swimming – A Rapid Ethnographic Study, Mark A. Christie, David Elliott

International Journal of Aquatic Research and Education

Open water swimming (OWS) has rapidly grown in popularity, driven by the purported health benefits of cold-water immersion. A paucity of research remains specifically considering the notable risks inherent in OWS participation, and a lack of qualitative research on freshwater swimming experiences, and safety-related issues therein. This rapid ethnographic study, based at a dedicated OWS lake in the UK, conducted semi-structured interviews with OWS participants (n=17; female=11, male=6). Two core themes emerged: environmental issues impacting OWS experiences and behaviours; and knowledge and education of OWS which highlighted safe/unsafe practices, levels of education for managing risks, personal preparedness, swimming solo/with others, …

Comparison Of Raw Accelerometry Data From Actigraph, Apple Watch, Garmin, And Fitbit Using A Mechanical Shaker Table, James W. White Iii, Olivia L. Finnegan, Nick Tindall, Srihari Nelakuditi, David E. Brown Iii, Russell R. Pate Ph.D., Gregory J. Welk, Massimiliano De Zambotti, Rahul Ghosal, Yuan Wang, Sarah Burkart, Elizabeth L. Adams, Mvs Chandrashekhar, Bridget Armstrong, Michael W. Beets, Robert Weaver Med, Phd

Faculty Publications

The purpose of this study was to evaluate the reliability and validity of the raw accelerometry output from research-grade and consumer wearable devices compared to accelerations produced by a mechanical shaker table. Raw accelerometry data from a total of 40 devices (i.e., n = 10 ActiGraph wGT3X-BT, n = 10 Apple Watch Series 7, n = 10 Garmin Vivoactive 4S, and n = 10 Fitbit Sense) were compared to reference accelerations produced by an orbital shaker table at speeds ranging from 0.6 Hz (4.4 milligravity-mg) to 3.2 Hz (124.7mg). Two-way random effects absolute intraclass correlation coefficients (ICC) tested inter-device reliability. …

Lay Rescuer Equipment Preferences And Efficacy During A Simulated Drowning Event, Alison M. Miller, William D. Ramos, Kristina R. Anderson, Jill Cuvala

International Journal of Aquatic Research and Education

During a drowning incident where a lifeguard is not present, a bystander – referred to as a lay rescuer - may put themselves in danger by attempting a rescue. When lay rescuers can avoid entering the water by using rescue equipment to help a drowning victim, it serves to not only help the person actively drowning, but also provides a layer of protection to a lay rescuer. This study sought to examine the following questions: (a) which pieces of rescue equipment were preferred by lay rescuers at pre-determined short and long distances, (b) do lay rescuers select appropriate rescue equipment …

Barriers: Location, Functionality, And Method Of Access In Childhood Pool/Spa Submersion Incidents, United States, 2000-2017, Alison Miller, Kristina R. Anderson, William D. Ramos

International Journal of Aquatic Research and Education

Drowning is a leading cause of fatality among children in the United States, and residential pools/spas currently account for as much as 80% of these submersion incidents. This study reviewed narrative case reports obtained from the United States Consumer Product Safety Commission (CPSC) to understand barrier location, type, and functionality as methods of pool/spa access for childhood submersion incidents. Retroactive analysis of 1,523 fatal and non-fatal submersion incidents among children aged 13 years old and younger was conducted using the CPSC in depth investigation dataset from 2000-2017. Narrative descriptions were coded according to the attributes of barrier location, functionality, and …

Perceived And Real Water Competency And Drowning Risk Among Adults, Teresa Stanley, Kevin Moran, Dawn Garbett, Alan Ovens

International Journal of Aquatic Research and Education

Traditionally, public understanding of drowning survival has focused on swimming capacity, often measured by how far a person can swim. With respect to the high incidence of adult drowning in high-income countries, using the more inclusive concept of water competency may yield a more comprehensive explanatory framework for understanding the reasons behind these drownings. Any competency base required to survive a drowning situation is dynamic, complex, and multi-faceted. Furthermore, perceptions of risk and capacity to cope with that risk are likely to be pivotal to the avoidance of drowning. Adults’ perceived water competence was measured against their actual water competence …

High Dietary Folic Acid Supplementation Reduced The Composition Of Fatty Acids And Amino Acids In Fortified Eggs, Ao-Chuan Yu, Yu-Han Deng, Cheng Long, Xi-Hui Sheng, Xiang-Guo Wang, Long-Fei Xiao, Xue-Ze Lv, Xiang-Ning Chen, Li Chen, Xiao-Long Qi

Faculty, Staff and Student Publications

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs.

METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were …

Activation Of Endogenous Retroviruses And Induction Of Viral Mimicry By Mek1/2 Inhibition In Pancreatic Cancer, Alice Cortesi, Francesco Gandolfi, Fabiana Arco, Pierluigi Di Chiaro, Emanuele Valli, Sara Polletti, Roberta Noberini, Francesco Gualdrini, Sergio Attanasio, Francesca Citron, I-Lin Ho, Rutvi Shah, Er-Yen Yen, Mara Cetty Spinella, Simona Ronzoni, Simona Rodighiero, Nico Mitro, Tiziana Bonaldi, Serena Ghisletti, Silvia Monticelli, Andrea Viale, Giuseppe Riccardo Diaferia, Gioacchino Natoli

Faculty, Staff and Student Publications

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes. We tracked ERV activation …

Visual Analysis Of Bone Malignancies Immunotherapy: A Bibliometric Analysis From 2010 To 2023, Kaiyu Shen, Liu Yang, Shuaiyi Ke, Wencang Gao

Faculty, Staff and Student Publications

Background: Bone malignancies (BM), including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and chordoma, are characterized by high rates of recurrence and mortality, despite the availability of diverse treatment approaches. Immunotherapy has gained increasing importance in cancer treatment. However, there is a lack of comprehensive studies that utilize bibliometric analysis to explore immunotherapy for BM.

Methods: A literature search of English studies on BM and immunotherapy from 2010 to 2023 was conducted in the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were utilized to examine global trends and research hotspots in this field.

Results: …

Pre-Covid-19 Hospital Quality And Hospital Response To Covid-19: Examining Associations Between Risk-Adjusted Mortality For Patients Hospitalised With Covid-19 And Pre-Covid-19 Hospital Quality, Doris Peter, Shu-Xia Li, Yongfei Wang, Jing Zhang, Jacqueline Grady, Kerry Mcdowell, Erica Norton, Zhenqiu Lin, Susannah Bernheim, Arjun K Venkatesh, Lee A Fleisher, Michelle Schreiber, Lisa G Suter, Elizabeth W Triche

Faculty, Staff and Student Publications

OBJECTIVES: The extent to which care quality influenced outcomes for patients hospitalised with COVID-19 is unknown. Our objective was to determine if prepandemic hospital quality is associated with mortality among Medicare patients hospitalised with COVID-19.

DESIGN: This is a retrospective observational study. We calculated hospital-level risk-standardised in-hospital and 30-day mortality rates (risk-standardised mortality rates, RSMRs) for patients hospitalised with COVID-19, and correlation coefficients between RSMRs and pre-COVID-19 hospital quality, overall and stratified by hospital characteristics.

SETTING: Short-term acute care hospitals and critical access hospitals in the USA.

PARTICIPANTS: Hospitalised Medicare beneficiaries (Fee-For-Service and Medicare Advantage) age 65 and older hospitalised …

Ndrgs In Breast Cancer: A Review And In Silico Analysis, Emilly S Villodre, Anh P N Nguyen, Bisrat G Debeb

Faculty, Staff and Student Publications

Simple Summary

Breast cancer is the most common cancer in women and one of the deadliest. While survival rates for patients with breast cancer have seen notable improvements in recent decades, current treatment strategies still face significant limitations, especially for patients with aggressive, therapy-resistant, and metastatic breast cancers. For this reason, it is important to identify new targets in order to develop more effective therapeutic strategies. The N-myc downstream regulated gene family (NDRGs), comprising NDRG1, NDRG2, NDRG3, and NDRG4, has been previously described as tumor suppressors. However, recent findings challenge this perception, particularly for NDRG1, …

Regional Analysis To Delineate Intrasample Heterogeneity With Regionalst, Yue Lyu, Chong Wu, Wei Sun, Ziyi Li

Faculty, Staff and Student Publications

MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human diseases. Intra-tumor heterogeneity, e.g. may be associated with cancer treatment responses. However, the lack of computational tools for exploiting cross-regional information and the limited spatial resolution of current technologies present major obstacles to elucidating tissue heterogeneity.

RESULTS: To address these challenges, we introduce RegionalST, an efficient computational method that enables users to quantify cell type mixture and interactions, identify sub-regions of interest, and perform cross-region cell type-specific differential analysis for the first time. Our simulations …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissuejove: Peer Reviewed Scientific Video Journal Article Protocols, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Faculty, Staff and Students Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Admix-Kit: An Integrated Toolkit And Pipeline For Genetic Analyses Of Admixed Populations, Kangcheng Hou, Stephanie Gogarten, Joohyun Kim, Xing Hua, Julie-Alexia Dias, Quan Sun, Ying Wang, Taotao Tan, Elizabeth G Atkinson, Alicia Martin, Jonathan Shortt, Jibril Hirbo, Yun Li, Bogdan Pasaniuc, Haoyu Zhang

Faculty, Staff and Students Publications

SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations.

AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissue, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

The Significance Of Using Digital Story-Telling For Enhancing English Oral Communication Skills Among Media Students At Al- Quds Open University, Murad A. Ahmed Tamimi

Middle East Journal of Communication Studies

Due to issues including uninspired teaching techniques and language anxiety, students at Al-Quds Open University, particularly those enrolled in the media major, experience difficulties in establishing strong oral communication skills in a multicultural context. A potential remedy is digital story-telling, which uses multimedia to craft captivating stories that appeal to students who are accustomed to using digital devices. This study evaluated how digital story-telling improved media students' spoken English communication abilities in the second semester of the 2023–2024 academic year. Incorporating motifs from the current Tufan al-Aqsa conflict, the study sought to offer stimulating and culturally appropriate educational opportunities. Twenty-seven …

Interest In An Instagram-Delivered Gestational Weight Gain Intervention Among Pregnant Women With Pre-Pregnancy Overweight Or Obesity, Molly E. Waring, Danielle Arigo, Lauren R. Rudin, Sherry L. Pogoto, Tiffany A. Moore Simas, Alexa B. Horkachuck

College of Science & Mathematics Departmental Research

Background: Barriers to attending in-person lifestyle interventions are common during pregnancy. The majority of young adults use Instagram, and pregnancy-related content abounds on this social media platform. The aims of this study were to assess interest in an Instagram-delivered gestational weight gain (GWG) intervention, examine characteristics associated with program interest, describe interest in specific program components, and to explore perceived advantages of and concerns about the proposed intervention. Methods: English-speaking pregnant women with pre-pregnancy overweight or obesity in the US who use Instagram completed a cross-sectional online survey (N=229). Participants reported interest in a proposed Instagram-delivered GWG intervention (very/quite a …

Safety Of Potentised Dilutions Of Rhus Toxicodendron In Wistar Albino Rats, Abanti Goswami, Narasimha Kumar Gv, Vara Prasad Saka, Pankaj Gupta, Bibaswan Biswas, Digvijay Verma

Indian Journal of Research in Homoeopathy

Background: Rhus toxicodendron (Rhus tox.) is a well-known homoeopathic medicine used to treat inflammatory disorders supported by historical and modern scientific evidence. Objective: The safety testing of 6C, 30C and 200C potencies of Rhus tox. through acute and sub-acute oral toxicity tests as per the Organisation for Economic Cooperation and Development test guidelines. Methods: For the acute oral toxicity study, Rhus tox. (2000 μL/kg) was administered to rats and observed for 14 days. For the subacute oral toxicity study, Rhus tox. (200 μL/kg) was administered for 28 days and additional recovery groups were included to monitor reversibility, persistence, or delayed …

Cancer Biomarkers: Emerging Trends And Clinical Implications For Personalized Treatment, Antonio Passaro, Maise Al Bakir, Emily G Hamilton, Maximilian Diehn, Fabrice André, Sinchita Roy-Chowdhuri, Giannis Mountzios, Ignacio I Wistuba, Charles Swanton, Solange Peters

Faculty, Staff and Student Publications

The integration of cancer biomarkers into oncology has revolutionized cancer treatment, yielding remarkable advancements in cancer therapeutics and the prognosis of cancer patients. The development of personalized medicine represents a turning point and a new paradigm in cancer management, as biomarkers enable oncologists to tailor treatments based on the unique molecular profile of each patient's tumor. In this review, we discuss the scientific milestones of cancer biomarkers and explore future possibilities to improve the management of patients with solid tumors. This progress is primarily attributed to the biological characterization of cancers, advancements in testing methodologies, elucidation of the immune microenvironment, …

Sans-Cnn: An Automated Machine Learning Technique For Spaceflight Associated Neuro-Ocular Syndrome With Astronaut Imaging Data, Sharif Amit Kamran, Khondker Fariha Hossain, Joshua Ong, Nasif Zaman, Ethan Waisberg, Phani Paladugu, Andrew G Lee, Alireza Tavakkoli

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the largest physiologic barriers to spaceflight and requires evaluation and mitigation for future planetary missions. As the spaceflight environment is a clinically limited environment, the purpose of this research is to provide automated, early detection and prognosis of SANS with a machine learning model trained and validated on astronaut SANS optical coherence tomography (OCT) images. In this study, we present a lightweight convolutional neural network (CNN) incorporating an EfficientNet encoder for detecting SANS from OCT images titled "SANS-CNN." We used 6303 OCT B-scan images for training/validation (80%/20% split) and 945 for testing …

Gpr56 In Gvl: Marker Or Mechanism?, Audra N Iness, Pavan Bachireddy

Faculty, Staff and Student Publications

No abstract provided.

Embracing Cancer Complexity: Hallmarks Of Systemic Disease, Charles Swanton, Elsa Bernard, Chris Abbosh, Fabrice André, Johan Auwerx, Allan Balmain, Dafna Bar-Sagi, René Bernards, Susan Bullman, James Degregori, Catherine Elliott, Ayelet Erez, Gerard Evan, Mark A Febbraio, Andrés Hidalgo, Mariam Jamal-Hanjani, Johanna A Joyce, Matthew Kaiser, Katja Lamia, Jason W Locasale, Sherene Loi, Ilaria Malanchi, Miriam Merad, Kathryn Musgrave, Ketan J Patel, Sergio Quezada, Jennifer A Wargo, Ashani Weeraratna, Eileen White, Frank Winkler, John N Wood, Karen H Vousden, Douglas Hanahan

Faculty, Staff and Student Publications

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the underlying causes of cancer-related death remains incomplete. Looking forward, elucidating how tumors interact with distant organs and how multifaceted environmental and physiological parameters impinge on tumors and their hosts will be crucial for advances in preventing and more effectively treating human cancers. In this perspective, we discuss complexities of cancer as a systemic disease, including tumor initiation and promotion, tumor micro- and immune macro-environments, aging, metabolism …

Antitumor Efficacy And Safety Of Unedited Autologous Cd5car T Cells In Relapsed/Refractory Mature T-Cell Lymphomas, Laquisa C Hill, Rayne H Rouce, Mengfen J Wu, Tao Wang, Royce Ma, Huimin Zhang, Birju Mehta, Natalia Lapteva, Zhuyong Mei, Tyler S Smith, Lina Yang, Madhuwanti Srinivasan, Phillip M Burkhardt, Carlos A Ramos, Premal Lulla, Martha Arredondo, Bambi Grilley, Helen E Heslop, Malcolm K Brenner, Maksim Mamonkin

Center for Medical Ethics and Health Policy Staff Publications

Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires additional gene modifications to overcome fratricide because of shared T-cell antigens on normal and malignant T cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels in transduced T cells while retaining strong cytotoxicity against CD5⁺ malignant cells. In our first-in-human phase 1 study (NCT0308190), second-generation autologous CD5.CAR T cells were manufactured from patients with r/r T-cell malignancies. Here, we report safety …