T cells expressing CD26-specific chimeric antigen receptors exhibit extensive self-antigen-driven fratricide

Abstract

Background: Immunotherapy utilizing T cells genetically modified to express chimeric antigen receptors (CARs) is rapidly emerging as a promising novel treatment for hematological and nonhematological malignancies. In order to target the TKI-insensitive leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) by CAR T cells, we chose CD26 as a cell surface tumor-associated antigen due to preferentially expression on LSCs. Additionally, CD26 has also been suggested to be a multipurpose therapeutic target for other cancer. Therefore, developing the CD26-targeting CAR T cells may be a promising therapy for not only LSCs but also other CD26+ cancer cells.

Methods: We designed the second-generation CD26-targeting CAR utilizing 4-1BB (CD137) as costimulatory domain, and transduced T cells with CD26-CAR containing lentiviral. Then we evaluated the transduction efficiency and expansion ability, and demonstrated the existence of self-antigen-driven fratricide by cytokine assay and cytotoxicity assay.

Results: Anti-CD26-4-1BB-CAR T cells exhibited poor viability, multiple cytokine secretion, down-regulation of CD26 and direct cytotoxicity against themselves, indicating self-antigen-driven fratricide.

Conclusion: Eradicating CML-LSCs via anti-CD26-4-1BB-CAR T cells is not applicable, and optimized design or alternative target is needed.     

结核分枝杆菌感染T细胞斑点试验的临床应用价值

目的 寻找一种敏感度和特异度都较高的临床诊断方法,以提高结核病的确诊率.方法 搜集110例经实验室与临床诊断确诊的患者,采用结核分枝杆菌感染T淋巴细胞斑点试验(T-SPOT.TB),检测其诊断结核病的敏感度和特异度.同时行PPD试验的患者104例.结果 66例结核患者中56例T-SPOT.TB检测阳性,敏感度为84.85％；66例中61例作PPD试验,42例为阳性结果,敏感度为68.85％,两者比较差异有统计学意义(x2=7.76,P＜0.05)；44例非结核性疾病患者中39例T-SPOT.TB检测阴性,特异度为88.64％；44例中43例作PPD试验,31例阴性,特异度为72.09％,两者比较差异有统计学意义(x2=4.72,P＜0.05).T-SPOT.TB检测在敏感度、特异度上均显著优于临床常用的PPD.T-SPOT.TB阳性预测值91.80％(56/61). PPD试验阳性预测值76.36％(42/55).结论 T-SPOT.TB试剂盒在检测结核病诊断方面具有很高的应用价值.     

阴茎背神经离断术联合α1受体阻断药治疗早泄的疗效

目的探讨阴茎背神经离断术联合高选择性α1受体阻断药治疗早泄的疗效。方法对89例早泄患者随机分为3组:单纯药物治疗组、单纯阴茎背神经离断组、联合治疗组,每组给予相应治疗,观察阴道内射精潜伏期的变化。结果联合治疗组阴道内射精潜伏期(160.4±57.7 s)较单纯药物α1受体阻断药治疗组(64.3±23.2 s)和单纯阴茎背神经离断组(106.5±41.4 s)明显延长(P<0.01)。结论阴茎背神经离断术联合高选择性α1受体阻断药治疗早泄效果明显。     

IL-10-producing B cells involved in the pathogenesis of Coxsackie virus B3-induced acute viral myocarditis

Background: Interleukin-10 (IL-10)-producing B cells, a subset of regulatory B cells, play critical roles in autoimmune and infectious diseases. However, the role of IL-10-producing B cells in acute viral myocarditis (AVMC) remains unknown. Methods: BALB/c mice were intraperitoneally (i. p.) infected with coxsackievirus B3 (CVB3) to establish AVMC models (AVMC group), while control mice (control group) were treated with phosphate-buffered saline (PBS) i. p. According to the time after injection, the AVMC group mice or control group mice were randomly separated into 1 week and 2 week subgroup. Myocardial histopathological changes were observed by hematoxylin and eosin staining and the frequency of splenic IL-10-producing B cells was measured by flow cytometry. Results: Histopathologic examination of heart tissues showed that mice infected with CVB3 developed AVMC. Compared with control group, the frequency of splenic IL-10-producing B cells was increased significantly in the AVMC group, with the 1 week AVMC subgroup (3.58 ± 0.47%) higher than the 2 week AVMC subgroup (2.50 ± 0.42%) (all P < 0.05). Conclusions: IL-10-producing B cells are increased in CVB3-induced AVMC, indicating that IL-10-producing B cells may play an important role in the pathogenesis of CVB3-induced AVMC.     

某军区总医院建设发展SWOT分析

对某军区总医院采取学科调研、座谈交流、纵横比较等方法,分析当前医院所处的各种环境因素,应用SWOT分析,提出中长期发展战略。     

超声造影对肝脏肿瘤诊断价值的Meta分析

目的分析超声造影对肝脏肿瘤诊断价值的Meta评分。方法选取我院肝脏肿瘤疾病患者31例进行研究,采用超声造影进行诊断,进行Meta评分。结果 对患者进行阈值效应检验审查,如出现阈值效应现象,其敏感度数值与其阴性、阳性存在联系,此外特异性与阳性存在联系,31例患者中,肝血管瘤占93.54%,肝细胞癌占96.77%,肝转移瘤占96.77%,肝内胆管癌占93.54%,数据显示采用超声造影对患者进行诊断具备较高准确率。结论 采用超声造影进行诊断具备较强的敏感性。     

Comparative study of CD4 and CD45RO T cells and CD20 B cells in cerebrospinal fluid of syphilitic meningitis and tuberculous meningitis patients

This study was to investigate the differences of lymphocyte in the cerebrospinal fluid (CSF) of patients with syphilis meningitis (SM) and tuberculous meningitis (TBM) for new diagnostic insights. Totally, 79 cases of SM and 45 cases of TBM were enrolled. In the CSF, the CD4, CD45RO or CD20 positive lymphocytes were detected by immunohistochemistry. The proportion of CD4 T cells in the CSF lymphocytes in patients with SM was significantly higher than that in patients with TBM (p < 0.05). After medical therapy, there was a significantly decline trend of the CD4 T‐cell proportion in both groups (p < 0.05). The proportion of CD45RO T cells in CSF lymphocytes of patients with SM was less than that of patients with TBM (p < 0.05). After medical therapy, the positive ratio of CD45RO T cells was increased in the CSF of both group patients (p < 0.05). The proportion of CD20B cells in the CSF lymphocytes was not obviously different between the two groups during every stage. In conclusion, there are strong differences of CD4 and CD45RO T‐cell ratio, but not the CD20 B cells in the meningitis. CD4 and CD45RO T cells in CSF are a useful complement in differentially diagnosing SM and TBM; it contributes to further understand the pathogenesis and prognosis of SM and TBM.