Summit on cell therapy for cancer: The importance of the interaction of multiple disciplines to advance clinical therapy

The field of cellular therapy of cancer is moving quickly and the issues involved with its advancement are complex and wide ranging. The growing clinical applications and success of adoptive cellular therapy of cancer has been due to the rapid evolution of immunology, cancer biology, gene therapy and stem cell biology and the translation of advances in these fields from the research laboratory to the clinic. The continued development of this field is dependent on the exchange of ideas across these diverse disciplines, the testing of new ideas in the research laboratory and in animal models, the development of new cellular therapies and GMP methods to produce these therapies, and the testing of new adoptive cell therapies in clinical trials. The Summit on Cell Therapy for Cancer to held on November 1 and 2, 2011 at the National Institutes of Health (NIH) campus will include a mix of perspectives, concepts and ideas related to adoptive cellular therapy that are not normally presented together at any single meeting. This novel assembly will generate new ideas and new collaborations and possibly increase the rate of advancement of this field

Immunological and Clinical Effects of Vaccines Targeting p53-Overexpressing Malignancies

Approximately 50% of human malignancies carry p53 mutations, which makes it a potential antigenic target for cancer immunotherapy. Adoptive transfer with p53-specific cytotoxic T-lymphocytes (CTL) and CD4+ T-helper cells eradicates p53-overexpressing tumors in mice. Furthermore, p53 antibodies and p53-specific CTLs can be detected in cancer patients, indicating that p53 is immunogenic. Based on these results, clinical trials were initiated. In this paper, we review immunological and clinical responses observed in cancer patients vaccinated with p53 targeting vaccines. In most trials, p53-specific vaccine-induced immunological responses were observed. Unfortunately, no clinical responses with significant reduction of tumor-burden have occurred. We will elaborate on possible explanations for this lack of clinical effectiveness. In the second part of this paper, we summarize several immunopotentiating combination strategies suitable for clinical use. In our opinion, future p53-vaccine studies should focus on addition of these immunopotentiating regimens to achieve clinically effective therapeutic vaccination strategies for cancer patients

Antibodies against p53 are associated with poor prognosis of colorectal cancer.

Mutation of the p53 gene is a common event in colorectal cancer. This alteration can result in cellular accumulation of p53 and may also induce p53 antibodies. Accumulation of p53 in tumour cells has been associated with poor prognosis of colorectal cancer. We tested preoperative sera from 255 patients with colorectal cancer by enzyme-linked immunosorbent assay (ELISA). A total of 70.2% had reactivity that was higher than the 'low' control serum. Employing a cut-off level of 10% of the 'high' control sample, 25.5% of the patients were positive for p53 antibodies. The presence of p53 antibodies correlated with the following prognostic factors: histological differentiation grade, shape of the tumour, and tumour invasion into blood vessels. Patients with p53 antibodies were shown to have decreased survival and decreased disease-free survival. Specifically for patients with cancer stage A and B1 the presence of p53 antibodies selected a subgroup with poor prognosis

P17-23. Enhanced expression of HIV antigens and improved antigen presentation after infection with replication competent attenuated vaccinia virus in vitro

1 página.-- Presentación de póster presentation.-- Este artículo es parte del suplemento: AIDS Vaccine 2009.Peer reviewe

Arthritis by autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments

__Abstract__ T cell lines (B13, B19) were isolated from the lymph nodes of Lewis rats 12 days after an arthritogenic injection of cell wall fragments of Eubacterium aerofaciens (ECW), a major resident of the human intestinal flora. These cell wall fragments consist of peptidoglycan polysaccharide complexes (PPC). The cell lines that bear the helper phenotype were arthritogenic in knee or ankle joints upon intravenous injection into irradiated Lewis recipients. B13 was, however, not arthritogenic in irradiated F344 recipients that are largely RT1 identical. The arthritis induced in the knee joints of the irradiated Lewis rats was clearly shown by a 99mtechnetium-pertechnetate scanning technique and was confirmed histologically. In vitro the cell lines showed a proliferative response after stimulation with syngeneic spleen cells alone. The proliferation was significantly higher when bacterial PPC, isolated in soluble form from normal feces or ileostomy fluid were added. Recognition by B13 appeared to be MHC class II restricted. These results show that autoreactive T cell lines can be isolated from rats after injection of bacterial cell wall antigens and that these cell lines can be arthritogenic. This suggests a role for autoreactive T cells in the induction of bacterial cell wall arthritis and might give a clue for the arthritogenic properties of the normal human intestinal flora

Antigen-specific active immunotherapy for ovarian cancer

BACKGROUND: This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes. DATA COLLECTION AND ANALYSIS: Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS. MAIN RESULTS: We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile. AUTHORS' CONCLUSIONS: We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs

Експортно­імпортні операції в Чернігівській губернії на початку ХХ ст.

У статті на основі маловідомих фактів досліджується організація зовнішньої торгівлі в Чернігівській губернії Російської імперії на початку ХХ ст. Показані основні екпортно-імпортні операції, особливості економічного розвитку регіону.В научной статье на основании использования неизвестных ранее фактов исследуется организация внешней торговли в Черниговской губернии Российской империи в начале ХХ века. Показаны основные экспортно-импортные операции и особенности экономического развития региона.In scientific article author research the special organization of foreign trade in Chernigov’s region of Russian empire in the beginning of 20 century. Export-import operations and economic development had illustration in this work

The effect of the TIM program (Transfer ICU Medication reconciliation) on medication transfer errors in two Dutch intensive care units

__Background:__ The transfer of patients to and from the Intensive Care Unit (ICU) is prone to medication errors. The aim of the present study is to determine whether the number of medication errors at ICU admission and discharge and the associated potential harm and costs are reduced by using the Transfer ICU and Medication reconciliation (TIM) program. __Methods:__ This prospective 8-month observational study with a pre- and post-design will assess the effects of the TIM program compared with usual care in two Dutch hospitals. Patients will be included if they are using at least one drug before hospital admission and will stay in the ICU for at least 24 h. They are excluded if they are transferred to another hospital, admitted and discharged in the same weekend or unable to communicate in Dutch or English. In the TIM program, a clinical pharmacist reconciles patient's medication history within 24 h after ICU admission, resulting in a "best possible" medication history and presents it to the ICU doctor. At ICU discharge the clinical pharmacist reconciles the prescribed ICU medication and the medication history with the ICU doctor, resulting in an ICU discharge medication list with medication prescription recommendations for the general ward doctor. Primary outcome measures are the proportions of patients with one or more medication transfer errors 24 h after ICU admission and 24 h after ICU discharge. Secondary outcome measures are the proportion of patients with potential adverse drug events, the severity of potential adverse drug events and the associated costs. For the primary outcome relative risks and 95% confidence intervals will be calculated. __Discussion:__ Strengths of this study are the tailor-made design of the TIM program and two participating hospitals. This study also has some limitations: A potential selection bias since this program is not performed during the weekends, collecting of potential rather than actual adverse drug events and finally a relatively short study period. Nevertheless, the findings of this study will provide valuable information on a crucial safety intervention in the ICU