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  • 1
    Keywords: CANCER ; CELLS ; SURVIVAL ; ENDOTHELIAL GROWTH-FACTOR ; Germany ; IN-VIVO ; THERAPY ; PROTEIN ; PATIENT ; RESPONSES ; tumour ; T-CELL ; T-CELLS ; IMMUNE-RESPONSES ; RECOGNITION ; ACID ; metastases ; VACCINE ; graft-versus-leukemia ; STRATEGIES ; IMMUNE-RESPONSE ; IMMUNITY ; IMMUNOTHERAPY ; NEWCASTLE-DISEASE VIRUS ; CANCER PATIENTS ; COLONY-STIMULATING FACTOR ; adoptive immunotherapy ; SINGLE ; molecular ; oncolytic virus ; TRANSLATION ; AMINO-ACID ; ACTIVE-SPECIFIC IMMUNOTHERAPY ; DNA vaccine ; dendritic cell ; ABILITY ; PHASE-I TRIAL ; memory T cells ; BREAST-CANCER PATIENTS ; ALLOGENEIC BONE-MARROW ; AUTOLOGOUS TUMOR-CELLS ; immune T cells ; MINOR HISTOCOMPATIBILITY ANTIGENS ; tumour response ; tumour vaccine
    Abstract: Advances in cellular and molecular immunology have led to the development of strategies for effective augmentation of antitumour immune responses in cancer patients. This review focuses on the manipulation of T cell immunity either by active specific immunotherapy (ASI) using tumour vaccines, or by adoptive immunotherapy (ADI) with immune T cells. Such therapies offer exquisite specificity of tumour recognition based on the ability of the T cell to distinguish single amino acid differences in any protein from any compartment of the tumour cell. Examples are presented of clinical survival benefits for cancer patients by postoperative ASI with a modified autologous tumour vaccine of high quality. Furthermore, clinical studies employing ADI with T cells activated and expanded ex vivo have demonstrated 'proof of principle' that tumour-specific T cells are capable of mediating anticancer activity in vivo, as measured by regression of metastatic tumours. Translation of these findings into a standardised immunotherapy is, however, not easy and will require coordination and cooperation among academic, private and federal sectors
    Type of Publication: Journal article published
    PubMed ID: 16050783
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  • 2
    Keywords: GENE-EXPRESSION ; MONOCLONAL-ANTIBODY ; ANTITUMOR-ACTIVITY ; STEM-CELL TRANSPLANTATION ; PHASE-I TRIAL ; unfolded protein response ; LOW-DOSE DEXAMETHASONE ; ACTIVE PROTEASOME INHIBITOR ; BONE-MARROW MICROENVIRONMENT ; SINGLE-AGENT CARFILZOMIB
    Abstract: Introduction: The availability of thalidomide, lenalidomide, and bortezomib has radically changed multiple myeloma (MM) treatment and significantly improved patients' outcome. Nevertheless, MM is still an incurable disease due to the development of resistance and relapse practically in all patients. Unraveling MM pathogenesis, identifying prognostically high-risk patient populations, and optimizing current treatment strategies are among the challenges we are facing to reach a cure for this disease. Areas covered: This article reviews recent advances of the genomic analysis of malignant plasma cells and summarizes new insights into the pathophysiologic role of the MM microenvironment and the clinical assessment of derived novel therapeutic strategies. Moreover, current efforts to improve risk stratification and drug development are discussed, and most recent results of Phase II and III clinical trials that aim to optimize existing treatment regimens and to assess the next-generation anti-MM strategies are discussed. A systematic search was conducted of the Pubmed Medline, Embase, and Cochrane Library databases for primary articles, as well as of conference abstracts (e.g., of the American Society of Hematology, the American Society of Clinical Oncology, the American Association of Cancer Research, the European Hematology Association, and the Multiple Myeloma Workshop 2013), practice guidelines, and registries of clinical trials. Expert opinion: Given continuing advances to overcome current treatment challenges in MM, we are confident that long-lasting responses can be expected in many of our patients within the next decade.
    Type of Publication: Journal article published
    PubMed ID: 23768134
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  • 3
    Keywords: COLONY-STIMULATING FACTOR ; DUCTAL ADENOCARCINOMA ; PHASE-I/II TRIAL ; IMMUNE ACTIVATION ; REPLICATING ADENOVIRUS ; ONCOLYTIC MEASLES-VIRUS ; ALGENPANTUCEL-L IMMUNOTHERAPY ; STANDARD ADJUVANT THERAPY ; SECRETING TUMOR VACCINE ; PARVOVIRUS H-1PV
    Abstract: INTRODUCTION: The clinical outcomes of patients with pancreatic cancer are poor, and the limited success of classical chemotherapy underscores the need for new, targeted approaches for this disease. The delivery of genetic material to cells allows for a variety of therapeutic concepts. Engineered agents based on synthetic biology are under clinical investigation in various cancers, including pancreatic cancer. AREAS COVERED: This review focuses on Phase I - III clinical trials of gene and cell therapy for pancreatic cancer and on future implications of recent translational research. Trials available in the US National Library of Medicine ( www.clinicaltrials.gov ) until February 2014 were reviewed and relevant published results of preclinical and clinical studies were retrieved from www.pubmed.gov . EXPERT OPINION: In pancreatic cancer, gene and cell therapies are feasible and may have synergistic antitumor activity with standard treatment and/or immunotherapy. Challenges are related to application safety, manufacturing costs, and a new spectrum of adverse events. Further studies are needed to evaluate available agents in carefully designed protocols and combination regimens. Enabling personalized cancer therapy, insights from molecular diagnostic technologies will guide the development and selection of new gene-based drugs. The evolving preclinical and clinical data on gene-based therapies can lay the foundation for future avenues improving patient care in pancreatic cancer.
    Type of Publication: Journal article published
    PubMed ID: 25582170
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  • 4
    Keywords: CELLS ; SURVIVAL ; CELL ; CLINICAL-TRIAL ; Germany ; THERAPY ; SYSTEM ; SYSTEMS ; SITE ; SITES ; GENE ; GENES ; DRUG ; TISSUE ; gene therapy ; TRANSDUCTION ; gene transfer ; GENE-TRANSFER ; PATIENT ; SEQUENCE ; SEQUENCES ; treatment ; cytokines ; TARGET ; score ; TRIAL ; TRIALS ; VECTORS ; DESIGN ; resistance ; VECTOR ; CLINICAL-TRIALS ; chemotherapy ; genotoxicity ; REGION ; REGIONS ; SOFT ; PARAMETERS ; PROGENITOR CELLS ; SAFETY ; FREQUENT ; SELECTION ; INTEGRATION SITES ; adeno-associated virus-2 vector ; drug resistance ; DRUG-RESISTANCE ; EXPERIMENTAL BRAIN-TUMORS ; GENE-THERAPY ; HEMATOPOIETIC STEM-CELLS ; HERPES-SIMPLEX-VIRUS ; INTEGRATION SITE ; MARROW-REPOPULATING CELLS ; multidrug resistance-1 gene ; MULTIDRUG-RESISTANCE ; mutagenesis ; myeloprotective gene transfer ; PROJECT ; RECOMBINANT ADENOASSOCIATED VIRUS ; RESISTANCE MDR-1 GENE ; retroviral insertion ; retroviral vector ; RETROVIRAL VECTORS ; RETROVIRUS-MEDIATED TRANSFER ; SARCOMA ; SUICIDE GENE ; suicide gene transfm ; THYMIDINE KINASE GENE
    Abstract: Soft tissue sarcomas are a challenge for medical oncology and gene therapy. Protective and sensitising approaches that target normal and malignant tissue, respectively, both have their role for opening the therapeutic window. Recent data show that an intensive maintenance chemotherapy significantly reduces metastatic spread and improves disease-free survival in selected patient groups. However, delays of treatment due to cytopenia are frequent. Cytostatic drug resistance gene transfer to haematopoietic progenitor cells using retroviral vectors may allow further improvement of therapy results. In recent years, retroviral vector design, transduction techniques and engraftment capability of transduced cells have been optimised. Safety considerations of retroviral gene transfer have attracted public attention and can be addressed by analysis of genomic vector integration sites. A data bank project, 'retroviral insertion estimate of chromosomal integration' (RISC), containing 〉 200 integration sequences, has been set up by the authors' group to recognise critical genomic regions and genes involved with possible transforming capacity. Monitoring these parameters will allow the selection of the most suitable vectors for clinical application. Sarcoma cells seem to be highly susceptible to a variety of vectors, such as recombinant adeno-associated virus-2 (rAAV-2) vectors, adenoviral vectors or oncolytic herpes simplex viruses. Results from the first clinical trials with adenoviral vectors encoding for cytokines are promising. The other systems await further development towards clinical applications. Perspectives for further research are discussed in this review
    Type of Publication: Journal article published
    PubMed ID: 14640950
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  • 5
    Keywords: THERAPY ; COHORT ; QUALITY-OF-LIFE ; ANTI-IGE ; PERSISTENT ALLERGIC-ASTHMA ; PROTEIN-C DEFICIENCY ; EXHALED NITRIC-OXIDE ; EXCELS
    Abstract: Background: There have been concerns about the cardiovascular safety of omalizumab. Objectives: In this study, the clinical status of the omalizumab receiving severe asthma patients and the cytokine expressions patterns were investigated. Materials and methods: In a pilot study described below we examined the levels of serum eosinophil cationic peptid (ECP), CD200, d-dimer, 25-hydroxyvitamin D (25(OH) D), CXCL8 and IL-1 beta in asthma patients treated with anti-IgE therapy, to explore their relationship with disease activity, and the impact of anti-IgE therapy impact on those levels. Exercise stress testing and blood samples were taken at all follow up visits from the time of first diagnosis and after 20 months of treatment during the disease remission. Results: Fractional exhaled nitric oxide concentrations and serum levels of sTRAIL, sCD200, D-dimer, ECP, total IgE, IL-1 beta and Hs-CRP were decreased while CXCL8, 25(OH) D were increased after starting the treatment of anti-IgE. Our first case of a patient, who had both protein C and S deficiency and hence a high risk for thromboembolism, documents for the first time the safety of omalizumab for asthmatic patients with concurrent risk factors contributing to arteriothrombotic events. Conclusion: Omalizumab might be used carefully in patients with cardiovascular diseases.
    Type of Publication: Journal article published
    PubMed ID: 23883435
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