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David Bassan Yosi Meir Gozlan Adi Sharbi-Yunger Esther Tzehoval Lea Eisenbach 《International journal of cancer. Journal international du cancer》2019,145(10):2816-2826
Adoptive transfer of T cells that have been genetically modified to express an antitumor T-cell receptor (TCR) is a potent immunotherapy, but only if TCR avidity is sufficiently high. Endogenous TCRs specific to shared (self) tumor-associated antigens (TAAs) have low affinity due to central tolerance. Therefore, for effective therapy, anti-TAA TCRs with higher and optimal avidity must be generated. Here, we describe a new in vitro system for directed evolution of TCR avidity using somatic hypermutation (SHM), a mechanism used in nature by B cells for antibody optimization. We identified 44 point mutations to the Pmel-1 TCR, specific for the H-2Db-gp10025-33 melanoma antigen. Primary T cells transduced with TCRs containing two or three of these mutations had enhanced activity in vitro. Furthermore, the triple-mutant TCR improved in vivo therapy of tumor-bearing mice, which exhibited improved survival, smaller tumors and delayed or no relapse. TCR avidity maturation by SHM may be an effective strategy to improve cancer immunotherapy. 相似文献
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Joshua Demb Esther K. Wei Monika Izano Stephen Kritchevsky Helen Swede Anne B. Newman Michael Shlipak Tomi Akinyemiju Steven Gregorich Dejana Braithwaite 《Journal of Geriatric Oncology》2019,10(2):265-271
Objectives
We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.Methods
We fitted multivariable Cox models to assess whether circulating levels of inflammation markers were associated with incident lung cancers in the Health Aging, Body and Composition (HealthABC) prospective cohort of 3075 older adults aged 70–79?years at baseline. IL-6 and CRP were measured biennially, whereas TNF-α was measured at baseline.Results
Baseline levels of IL-6 were significantly associated with incident lung cancer risk in a model that adjusted for age, gender, race, and site (Model 1) (Hazard RatioT3 vs. T1: 3.34, 95% Confidence Interval: 1.91, 5.85) and in a model adjusted for health factors linked to chronic inflammation (Model 2) (HR T3 vs. T1: 2.57, 95% CI: 1.41, 4.65). The associations observed in time-updated IL-6 (HR T3 vs. T1: 2.47, 95% CI: 1.43, 4.28), cumulatively averaged IL-6 (HR T3 vs. T1: 2.47, 95% CI: 1.43, 4.35), and baseline CRP levels (HR T3 vs. T1: 1.85, 95% CI: 1.11, 3.08) with incident lung cancer in Model 1 were not statistically significant in Model 2.Conclusions
Baseline CRP and IL-6 levels were associated with increased risk of lung cancer in Model 1 and both models, respectively. Chronic IL-6 inflammation, as quantified by repeated measures was associated with incident lung cancer in Model 1, but not Model 2. Further research is needed to understand the role of CRP and IL-6 in lung carcinogenesis. 相似文献4.
Juan Faura-Garcia Izaskun Orue Esther Calvete 《Clinical psychology & psychotherapy》2021,28(4):739-765
There has been an increase in the number of assessment instruments for non-suicidal self-injury (NSSI). However, previous reviews are inconsistent and do not provide a comprehensive psychometric assessment of the instruments. This study aimed to systematically assess and compare the psychometric properties of clinically relevant instruments to measure NSSI in any population. Through a systematic review guided by COSMIN and PRISMA, two searches were conducted in English and Spanish in February 2020 in 13 databases including grey literature. Of the 7,813 initial records, 152 validations were extracted. From these, 83 instruments (22 versions or adaptations) were excluded for not measuring NSSI, having no potential clinical utility or not including psychometric properties. Finally, 26 (22 versions, 35 adaptations and 19 creations) instruments measuring NSSI were included. Predominantly, the studies were North American self-reports in English for community adolescents, adaptations or versions emanating from a small number of instruments. Twenty-six indicators were categorized to assess NSSI. The most frequent instruments are structured interviews, and their indicators were related to NSSI function and topography. Evidence of validity and reliability was positive but limited. Despite the high number of instruments and diversity of evaluations, we found no instrument with sufficient evidence for clinical assessment. Findings broadly overview NSSI assessment instruments' current use and future improvement in clinical and research settings. 相似文献
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Tsang Vionna M. W. Verlinden Eva van Duin Esther M. Twisk Jos W. R. Brilleslijper-Kater Sonja N. Gigengack Maj R. Verhoeff Arnoud P. Lindauer Ramón J. L. 《Child psychiatry and human development》2021,52(5):891-902
Child Psychiatry & Human Development - Longitudinal research of CSA in infancy and early childhood is scarce. The current study examined the long-term course of psychological outcomes (PTSD,... 相似文献
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