Phase-I study of Innacell γδ™, an autologous cell-therapy product highly enriched in γ9δ2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma

PURPOSE: gamma9delta2 T lymphocytes have been shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes T gammadelta can be selectively expanded in vivo with BrHPP (IPH1101, Phosphostim) and interleukin 2 (IL-2). A phase I Study was conducted in patients with metastatic renal cell carcinoma (mRCC) to determine the maximum-tolerated dose and safety of Innacell gammadeltatrade mark, an autologous cell-therapy product based on gamma9delta2 T lymphocytes, in patients with mRCC. EXPERIMENTAL DESIGN: A 1-h intravenous infusion of gamma9delta2 T lymphocytes was administered alone during treatment cycle 1 and combined with a low dose of subcutaneous interleukin-2 (IL-2, 2 MIU/m(2) from Day 1 to Day 7) in the two subsequent cycles (at 3-week intervals). The dose of gamma9delta2 T lymphocytes was escalated from 1 up to 8 x 10(9) cells. RESULTS: Ten patients underwent a total of 27 treatment cycles. Immunomonitoring data demonstrate that gamma9delta2 T lymphocytes are initially cleared from the blood to reappear at the end of IL-2 administration. Dose-limiting toxicity occurred in one patient at the dose of 8 x 10(9) cells (disseminated intravascular coagulation). Other treatment-related adverse events (AEs) included mainly gastrointestinal disorders and flu-like symptoms (fatigue, pyrexia, rigors). Hypotension and tachycardia also occurred, especially with co-administered IL-2. Six patients showed stabilized disease. Time to progression was 25.7 weeks. CONCLUSION: The data collected in ten patients with mRCC indicate that repeated infusions of Innacell gammadeltatrade mark at different dose levels (up to 8 x 10(9) total cells), either alone or with IL-2 is well tolerated. These results are in favor of the therapeutic value of cell therapy with Innacell gammadeltatrade mark for the treatment of cancers.     

Are Circadian Rhythms the Code of Hypothalamic-Immune Communication? Insights from Natural Killer Cells

Circadian rhythms in physiology and behavior are ultimately regulated at the hypothalamic level by the suprachiasmatic nuclei (SCN). This central oscillator transduces photic information to the cellular clocks in the periphery through the autonomic nervous system and the neuroendocrine system. The fact that these two systems have been shown to modulate leukocyte physiology supports the concept that the circadian component is an important aspect of hypothalamic-immune communication. Circadian disruption has been linked to immune dysregulation, and recent reports suggest that several circadian clock genes, in addition to their time-keeping role, are involved in the immune response. In this overview, we summarize the findings demonstrating that Natural Killer (NK) cell function is under circadian control. Special issue article in honor of George Fink.     

表达轮状病毒G2和G3型vp7基因重组腺病毒的免疫效果

为探索以非复制型腺病毒为表达载体的多价轮状病毒(Rotavirus,RV)基因工程疫苗的可行性,在前期工作的基础上,对表达我国G2和G3型RV流行毒株vp7基因的重组腺病毒的免疫效果进行了研究。分别用表达G2和G3型vp7基因的重组腺病毒rvAdG2VP7、rvAdG3VP7经滴鼻和灌胃两种途径免疫Balb/c小鼠,对免疫后小鼠的血清抗体、黏膜抗体和相关的细胞因子水平进行了检测和比较。结果表明,用表达G2和G3型vp7基因的重组腺病毒经滴鼻和灌胃两种途径免疫小鼠后,均可诱导机体产生较强的RV特异性免疫反应,包括体液免疫、细胞免疫和黏膜免疫,并能产生中和抗体。但免疫反应以Th2类为主,Th1类反应也占有相当的比例。本研究为新型RV基因工程疫苗的深入研究奠定了基础。     

蛇伤一号合剂的研制及临床应用

目的 研究蛇伤一号合剂的制备并观察其临床疗效。方法 以煎煮、浓缩法制备合剂,联合对症支持治疗毒蛇咬伤者3245例,口服合剂30ml／次,每天3次。结果 痊愈3152例,残愈29例,总有效率99．8％。结论 蛇伤一号合剂对各类毒蛇咬伤有较好疗效。     

Self‐Efficacy as a Predictor of Weight Change in African‐American Women

Objective: Although self‐efficacy has received increasing attention for its role in weight loss, there is less research examining this relationship in minority samples. The purpose of this study was to determine whether self‐efficacy for weight loss was predictive of weight change in a sample of African‐American women. Research Methods and Procedures: Subjects were 106 overweight or obese, low‐income African‐American women participating in a weight management intervention that involved either personalized monthly sessions with their primary care physician or standard care. Weight and self‐efficacy for weight loss were assessed at baseline and at the end of the 6‐month treatment. Results: For subjects in the personalized intervention, baseline self‐efficacy was predictive of subsequent weight change, such that higher levels of self‐efficacy before treatment were associated with less weight loss. In contrast, improvements in self‐efficacy during treatment were associated with greater weight loss for the personalized intervention group. Discussion: Results suggest high self‐efficacy for weight loss before treatment may be detrimental to success, whereas treatments that improve participants’ self‐efficacy may result in greater weight loss. High pretreatment self‐efficacy may be indicative of overconfidence or lack of experience with the difficulties associated with weight loss efforts. Whereas replication is needed, our results suggest that self‐efficacy is an important variable to consider when implementing weight loss interventions.     

田间应用拮抗酵母菌对甜樱桃果实采后病害的防治效果

研究了应用拮抗酵母菌丝孢酵母(Trichosporon pullulans(Lindner.)Diddens et Lodder)、罗伦隐球酵母(Cryptococcus laurentii(Kuffer.)Skinner)和粘红酵母(Rhodotorula glutinis(Fresenius)Harrison)后拮抗菌在果实表面的繁殖能力以及对不同贮藏条件下甜樱桃(Pranus avivum L.cv.Hongdeng)果实采后病害的防治效果。酵母菌的使用浓度为1×10~8CFU/mL。结果表明,田间3种拮抗菌都能够在果实表面增值,但是只有C.laurentii和R.glutinis能够持续稳定地生长。C.laurentii的抑病效果最好,它对田间环境和采后低温低氧及高CO_2都具有很强的适应能力。     

人狂犬病免疫球蛋白使用效果观察

为了解人狂犬病免疫球蛋白的作用效果,我们将观察对象随机分成了A、B、C三组,分别采用三种措施进行狂犬病的预防治疗,即：A组联合使用狂犬病疫苗与人狂犬病免疫球蛋白;B组联合使用狂犬病疫苗与抗狂犬病血清(马源);C组仅注射狂犬病疫苗,并采用小鼠中和试验对这三组成员在免疫后3、7、14、45天及1年时的中和抗体水平进行检测。结果表明：狂犬病疫苗与人狂犬病免疫球蛋白或抗狂犬病血清联合使用,可使体内更早出现抗狂犬病的中和抗体。注射人狂犬病免疫球蛋白后未发生临床副反应。     

TLR4 signaling in cancer cells promotes chemoattraction of immature dendritic cells via autocrine CCL20

Toll-like receptors (TLRs) are involved in the production of inflammatory mediators upon specific ligands stimuli. Chemokines are important inflammatory mediators capable of chemoattracting diverse immune cells. In addition to normal immune cells, the expression of TLRs and chemokines has been detected in various tumor cells. However, the roles of TLRs and chemokines expressed by tumor cells in the processes of tumor progression and immune escape have not been fully elucidated. Here we report that TLR4 ligation by lipopolysaccharide (LPS) significantly promotes CT-26 colon cancer cells to produce chemokine CCL20 via activation of TLR4 signaling pathways. We find that LPS treatment of CT-26 cells can significantly increase the chemoattraction of immature dendritic cells (DC) by the autocrine CCL20. Our studies suggest that TLR4 expressed by tumor cells may be involved in the induction of chemokines like CCL20, providing a potential linkage between chronic inflammation and tumor immune escape.     

柱状噬纤维菌免疫后兴国红鲤免疫细胞数量变化的研究

用柱状噬纤维菌灭活菌苗免疫兴国红鲤,于免疫后2周,4周分析对其外周血液和胸腺,脾脏,头肾和体肾中的免疫细胞数量变化进行了测定,结果显示：外周血液中,淋巴细胞有显著的增加,粒细胞和单核细胞有明显的下降,胸腺中淋巴细胞数目略有增加,脾脏中淋巴细胞有显著的增加,而粒细胞和单核细胞正相反,头肾中淋巴细胞有较多的增加,粒细胞数目增加不明显,单核细胞有大幅下降,体肾中,粒细胞和淋巴细胞大幅上升,单核细胞下降。