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BACKGROUND: T cells expressing antigen-specific chimeric antigen receptors (CARs) improve outcomes for CD19-expressing B cell malignancies. We evaluated a human application of T cells that were genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific CAR. METHODS: T cells were genetically modified using DNA plasmids from the SB platform to stably express a second-generation CD19-specific CAR and selectively propagated ex vivo with activating and propagating cells (AaPCs) and cytokines. Twenty-six patients with advanced non-Hodgkin lymphoma and acute lymphoblastic leukemia safely underwent hematopoietic stem cell transplantation (HSCT) and infusion of CAR T cells as adjuvant therapy in the autologous (n = 7) or allogeneic settings (n = 19). RESULTS: SB-mediated genetic transposition and stimulation resulted in 2,200- to 2,500-fold ex vivo expansion of genetically modified T cells, with 84% CAR expression, and without integration hotspots. Following autologous HSCT, the 30-month progression-free and overall survivals were 83% and 100%, respectively. After allogeneic HSCT, the respective 12-month rates were 53% and 63%. No acute or late toxicities and no exacerbation of graft-versus-host disease were observed. Despite a low antigen burden and unsupportive recipient cytokine environment, CAR T cells persisted for an average of 201 days for autologous recipients and 51 days for allogeneic recipients. CONCLUSIONS: CD19-specific CAR T cells generated with SB and AaPC platforms were safe, and may provide additional cancer control as planned infusions after HSCT. These results support further clinical development of this nonviral gene therapy approach. TRIAL REGISTRATION: Autologous, NCT00968760; allogeneic, NCT01497184; long-term follow-up, NCT01492036. FUNDING: National Cancer Institute, private foundations, and institutional funds. Please see Acknowledgments for details.

PurposeThis study evaluated the discriminatory power of salivary transcriptomic and proteomic biomarkers in distinguishing oral squamous cell carcinoma cases from controls and potentially malignant oral disorders (PMOD).Experimental designA total of 180 samples (60 OSCC patients, 60 controls, and 60 PMOD patients) were used in the study. Seven transcriptomic markers (IL8, IL1β, SAT1, OAZ1, DUSP1, S100P, and H3F3A) were measured using qPCR, and two proteomic markers (IL8 and IL1β) were evaluated by ELISA.ResultsAmong 7 transcriptomic markers, transcript level of DUSP1 was significantly lower in OSCC patients than in controls and PMOD patients. Between the proteomic markers, the protein concentration of IL8 and IL1β was significantly higher in OSCC patients than controls and dysplasia patients. Univariate fractional polynomial (FP) models revealed that salivary IL8 protein (IL8p) has the highest AUC value between OSCC patients and controls (0.74) and between OSCC and PMOD patients (0.72). Applying a 2-marker FP model, salivary IL8p combined with IL1β gave the best AUC value for discrimination between OSCC patients and controls, as well as the IL8p combined with H3F3A mRNA, which gave the best AUC value for discrimination between OSCC and PMOD patients. Multivariate models analysis combining salivary analytes and risk factor exposure related to oral carcinogenesis formed the best combinatory variables for differentiation between OSCC versus PMOL (AUC = 0.80), OSCC versus controls (AUC = 0.87), and PMOD versus controls (AUC = 0.78).ConclusionsThe combination of transcriptomic and proteomic salivary markers is of great value for oral cancer detection and differentiation from PMOD patients and controls. Clin Cancer Res; 22(13); 3340-7. ©2016 AACR.

Previous studies have suggested occurrence of altered serum glycan profiles in patients with lung cancer. Here, we aimed to determine the predictive value of serum glycans to distinguish non-small cell lung cancer (NSCLC) cases from controls in prediagnostic samples using a previously validated predictive protein marker pro-SFTPB, as anchor. Blinded prediagnostic serum samples were obtained from the Carotene and Retinol Efficacy Trial (CARET), and included a discovery set of 100 NSCLC cases and 199 healthy controls. A second test set consisted of 108 cases and 216 controls. Cases and controls were matched for age at baseline (5-year groups), sex, smoking status (current vs. former), study enrollment cohort, and date of blood draw. Serum glycan profiles were determined by mass spectrometry. Twelve glycan variables were identified to have significant discriminatory power between cases and controls in the discovery set (AUC > 0.6). Of these, four were confirmed in the independent validation set. A combination marker yielded AUCs of 0.74 and 0.64 in the discovery and test set, respectively. Four glycan variables exhibited significant incremental value when combined with pro-SFTPB compared with pro-SFTPB alone with AUCs of 0.73, 0.72, 0.72, and 0.72 in the test set, indicating that serum glycan signatures have relevance to risk assessment for NSCLC.

Context: Palliative, Rehabilitation, and Integrative Medicine (PRIM) department members anonymously reported a positive experience with work from home (WFH) two months after its rapid pandemic transition in March 2020. Data are limited on the stability of such preferences and experiences over time. Objectives: The objectives of this study were to survey the attitudes and beliefs of PRIM employees toward remote work 16 months after the start of the coronavirus disease 2019 (COVID-19) pandemic since vaccines and to determine changes in perceptions of WFH. Methods: All 138 PRIM employees were invited to participate in an anonymous survey from mid-July to mid-August 2021. The 30-question survey included demographics, perceptions toward WFH, and the pandemic. Results: One hundred fifteen (83%) employees completed the survey: 29 (74%) research, 62 (83%) clinicians, and 24 (100%) administrative personnel. Most were female (76%), 30–59 years old (88%), PRIM employees before May 2020 (89%), shared office space (52%), and had received either first or second dose of the COVID-19 vaccine (88%). Overall experience (86%) and emotional response (74%) with WFH were positive and not significantly different from 2020 (p = 0.128 and 0.782, respectively). Positive experience was associated with having adequate equipment (p = 0.002), perception of productivity (p = 0.002), financial advantage (p = 0.002), and time demands caring for dependents (p = 0.038). Clinicians reported less positive response (78%, p = 0.002) and less productivity (49%, p = 0.002) with WFH and higher level of stress (54%, p = 0.026) since COVID-19. Employees continued to support WFH permanently (79%) for two or more days/week (82%). There was continued increased emotional exhaustion (71%) similar to 2020 (p = 0.868), and being asked to work partially or completely from home permanently was favored by 64% versus 97% and 96% of clinicians, research, and administrative, respectively (p = 0.002). Conclusions: Support for WFH was sustained a year later and after three pandemic waves. These findings serve as a model for future rapid work transitions and can help elucidate factors associated with stress and emotional exhaustion in a new post-COVID-19 work environment. [ABSTRACT FROM AUTHOR]