参杞合剂对小鼠腹水型肝癌细胞株H22细胞周期及凋亡的影响

目的：观察参杞合剂(SQ)在体内、外对小鼠腹水型肝癌细胞株(HcaF16A3)细胞周期及凋亡的影响。方法：用SQ对荷瘤小鼠连续胃饲治疗10d，观察其NK细胞／Mφ的杀伤活性及细胞周期的改变。用流式细胞仪检测SQ对HcaF16A3细胞增殖的抑制作用与诱导凋亡的作用。结果：SQ的抑瘤率为65．68％。流式细胞仪检测发现，SQ可使肿瘤细胞的细胞周期阻滞到S期，并在体外诱导其凋亡。结论：SQ在体内、外均有抑瘤作用，其机制与细胞周期阻滞继而诱发凋亡有关。     

Exploiting T cell receptor genes for cancer immunotherapy

Adoptive antigen-specific immunotherapy is an attractive concept for the treatment of cancer because it does not require immunocompetence of patients, and the specificity of transferred lymphocytes can be targeted against tumour-associated antigens that are poorly immunogenic and thus fail to effectively trigger autologous T cell responses. As the isolation and in vitro expansion of antigen-specific lymphocytes is difficult, 'conventional' adoptive T cell therapy can only be carried out in specialized centres in small numbers of patients. However, T cell receptor (TCR) genes isolated from antigen-specific T cells can be exploited as generic therapeutic molecules for 'unconventional' antigen-specific immunotherapy. Retroviral TCR gene transfer into patient T cells can readily produce populations of antigen-specific lymphocytes after a single round of polyclonal T cell stimulation. TCR gene modified lymphocytes are functionally competent in vitro, and can have therapeutic efficacy in murine models in vivo. TCR gene expression is stable and modified lymphocytes can develop into memory T cells. Introduction of TCR genes into CD8(+) and CD4(+) lymphocytes provides an opportunity to use the same TCR specificity to produce antigen-specific killer and helper T lymphocytes. Thus, TCR gene therapy provides an attractive strategy to develop antigen-specific immunotherapy with autologous lymphocytes as a generic treatment option.     

A Double-Blind, Multicenter Immunotherapy Trial in Children, Using a Purified and Standardized Cladosporium herbarum Preparation II. In Vitro Results

This double-blind immunotherapy trial in children, using a purified and standardized Cladosporium herbarum allergen preparation, has shown that children with mould asthma and/or rhinoconjunctivitis, responded to immunotherapy with a decrease in specific IgE and a significant increase in specific IgG. There was a marked increase in the ratio specific IgG/specific IgE as a result of active treatment. IgE-CRIE radiostaining patterns showed no pronounced changes after 10 months' active treatment and no "new sensitivities" could be detected in the studied patients. IgG-CRIE radiostaining, primarily directed towards the important allergens, was significantly increased in the active group and particularly towards Ag-12 (partially identical to a previously described major allergen in Cladosporium herbarum, Ag-54). Children treated with histamine placebo showed no change in antibody patterns during 10 months of treatment.     

Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells

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Immunotherapy with partially purified and standardized tree pollen extracts

Patients allergic to pollen from alder, birch and hazel were hyposensitized during a 3-year period with either birch pollen extract alone (n = 24) or a mixture of one or more of alder, birch and hazel pollen extracts (n = 27). The effect of the treatment was evaluated by RAST and tandem crossed-radioimmunoelectrophoresis (tandem-CRIE). The patient' specific IgE response to the major allergens of alder (Aln g I), birch (Bet v I) and hazel (Cor a I and Cor a II), as measured by tandem-CRIE, and the total specific IgE response, measured by RAST, decreased significantly (Pc less than 0.05) during immunotherapy, irrespective of the extract used during the treatment. There was no significant difference (Pc less than 0.05) between the two treatment groups. The results obtained indicate either that birch pollen extract alone is adequate in the treatment of the studied patient group or the patients had been sensitized towards birch pollen alone.     

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage

Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful.     

Decreased production of CD8 (T8) antigen after immunotherapy

The working mechanism(s) of immunotherapy still remains ill defined. As T cells bearing CD8 antigen possess suppressor/cytotoxic function, this study was conducted to examine the effect of immunotherapy on the production of CD8 antigen. Peripheral blood mononuclear cells (MNC) were obtained from 21 newly diagnosed and 23 hyposensitized (>1 year) asthmatic children and 13 agematched normal children. MNC were stimulated with crude mite extract (Dermatophagoides farinae) for 7 days and with phytohemagglutinin and concanavalin A for 3 days. The CD8 antigen and interleukin-2 receptor (IL-2R) in plasmas and culture supernatants were measured by CELLFREE T8 and IL-2R test kits (T Cell Sciences, USA). The results showed the following. (1) Plasma CD8 antigen was markedly increased in new patients compared to normals (536.7 ± 212.3 vs 222.5 ± 104.0 units/ml;P<0.001) and decreased to normal after immunotherapy (275.7 ± 98.5 units/ml). (2) When stimulated with mite allergen, MNC from both new and hyposensitized patients produced a much greater amount of CD8 antigen compared to those from normals. However, after immunotherapy MNC tended to produce less CD8 antigen, although not to a significant degree. (3) No difference in CD8 antigen production was seen among three groups when lymphocytes were stimulated with mitogens. (4) Production of CD8 antigen paralleled that of IL-2R. Thus, CD8 production was specifically decreased after immunotherapy and this fact reflects a hyposensitized state of T cells after long-term, repeated injection of allergens.     

Cow’s Milk Protein Allergy as a Model of Food Allergies

Cow’s milk allergy (CMA) is one of the most common food allergies in infants, and its prevalence has increased over recent years. In the present paper, we focus on CMA as a model of food allergies in children. Understanding the diagnostic features of CMA is essential in order to manage patients with this disorder, guide the use of an elimination diet, and find the best moment to start an oral food challenge (OFC) and liberalize the diet. To date, no shared tolerance markers for the diagnosis of food allergy have been identified, and OFC remains the gold standard. Recently, oral immunotherapy (OIT) has emerged as a new therapeutic strategy and has changed the natural history of CMA. Before this, patients had to strictly avoid the food allergen, resulting in a decline in quality of life and subsequent nutritional, social, and psychological impairments. Thanks to the introduction of OIT, the passive approach involving rigid exclusion has changed to a proactive one. Both the heterogeneity in the diagnostic process among the studies and the variability of OIT data limit the comprehension of the real epidemiology of CMA, and, consequentially, its natural history. Therefore, well-planned randomized controlled trials are needed to standardize CMA diagnosis, prevention, and treatment strategies.     

BT—BAK细胞和BCG膀胱腔内过继免疫治疗对膀胱癌患者全身免疫功能影响的比较

目的：观察BT-BAK细胞与BCG膀胱腔内灌注治疗对患者全身免疫功能的影响。方法：由手术切除的膀胱瘤标本制备膀胱肿瘤可溶性抗原,以BCG为佐剂,从PBMNC中诱导出抗膀胱肿瘤特异性细胞毒性BT-BAK细胞,临床选择72例浅表性膀胱癌术后患者随机平均分成2组分别进行BT-BAK和BCG的膀胱腔内灌注治疗。于不同阶段采用ELISA法测定患者外周血中IL-2、TNF-α及IFN-γ的含量;观察治疗后患者PBMNC对T24膀胱肿瘤细胞株杀伤活性的变化。结果：BT-BAK组患者血清中IL-2、TNF-α及IFN-γ的水平均较治疗前明显提高（P＜0.01);患者PBMNC对T24膀胱肿瘤细胞株的杀伤活性显著增强（P＜0.01)。BT-BAK组上述指标均高于BCG组（P＜0.05)。平均随访18.16个月,两组的复发率分别为2.7%和11.11%。结论：BT-BAK细胞及其培养上清进行膀胱腔内灌注治疗,能够有效提高膀胱癌术后患者的全身免疫水平,降低膀胱癌的术后复发率。     

Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.