1,720,987 research outputs found
The detection and identification of nanoflagellates using fluorescent oligonucleotide probes
No full textSIGLEAvailable from British Library Document Supply Centre-DSC:DX190442 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
New strategies for vaccination and imunomodulation in NHL
No full textKnowledge of the genetic changes which occur in cancer cells is stimulating research aimed towards new therapies. Immunotherapeutic approaches, particularly antibody therapy, are already finding a place in treatment of hematological malignancies. Vaccination will build on experience in the field of infectious diseases, and it should be possible to design vehicles to deliver the expanding range of tumour antigens to the immune system. For DNA vaccines, fusion genes have the potential to activate and direct immune effector pathways. One candidate antigen for B-cell malignancies is the clonal idiotypic immunoglobulin and we have designed a fusion vaccine encoding idiotypic sequence fused to a sequence from a powerful antigen from tetanus toxin. This promotes protective immunity against lymphoma in models, and is now in clinical trial. Our challenge is to bring patients into remission without significant damage to immune capacity. Another is to rethink the nature of clinical trials so that more pilot studies of efficacy can be carried out. There is no evidence so far of toxicity due to injection of DNA, but for antigens which are expressed by normal cells, the line between attack on tumour and autoimmunity will have to be carefully drawn
A DNA vaccine strategy for effective antibody induction to pathogen-derived antigens
No full textDNA-based vaccines are currently being developed for treating a diversity of human diseases including cancers, autoimmune conditions, allergies, and microbial infections. In this chapter, we present a general protocol that can be used as a starting point for developing DNA vaccines to pathogen-derived antigens, using Neisseria meningitidis as an example. In addition, we describe a fusion gene-based vaccine protocol for increasing the potency of DNA vaccines that are based on poorly immunogenic antigens such as short pathogen-derived polypeptides. Finally, we provide a safe and effective protocol for delivery of DNA vaccines, based on intramuscular injection followed by electroporation
Commentary: Optimizing cancer immunotherapy trials: Back to basics
No full textAttempts to raise effective immunity against cancer are benefiting from information on the nature of the immunity involved and its regulation and, perhaps, now it is time to step back and define our approach in molecular terms prior to clinical testing. Although there are immunological differences between mice and patients, results from murine studies are encouraging early 'translation' of concepts to the clinic and it is vital to take immunological principles emerging from mice into clinical vaccine design. One is the requirement to break tolerance against over-expressed self-antigens, a potentially risky procedure but necessary for several cancer targets. A study in this issue of the European Journal of Immunology attempts to do this by using xenogeneic antigens, albeit with variable outcome. The unstated goal is to activate T-cell help but this can be achieved more effectively by harnessing a predictable anti-microbial repertoire. The second issue lies in the delivery of antigen. One strategy is "prime/boost" using DNA priming and boosting with a viral vector; however, this induces blocking immunity against viral proteins, and must be used judiciously. There are other physical methods to increase immunity such as electroporation, which can itself be used in 'prime/boost' sequence.. These twin problems of engagement of T-cell help and delivery of adequate antigen can now be addressed by applying immunological logic to cancer vaccines
DNA vaccines against cancer come of age
No full textGenetic technology allows construction of DNA vaccines encoding selected tumor antigens together with molecules to direct and amplify the desired effector pathways. Their enormous promise has been marred by a problem of scaling up to human subjects. This is now largely overcome by electroporation, which increases both antigen expression and the inflammatory milieu. While the principles of vaccine design can be developed in mouse models, the real operative test is in the clinic, using patients in temporary remission. Monitoring of induced immunity, although commonly limited to blood, is providing objective qualitative and quantitative data on T-cell and antibody responses. Prolongation of remission is the goal and an activated immune system should achieve thi
Tumor vaccines
No full textTumor vaccines able to deliver specific antigen to the immune system are now available and are beginning to stand the test of performance in human subjects. Target antigens are being defined, and sophisticated methods to measure induced specific responses are available. Initially, therefore, outcome is measurable in terms of immune parameters, This allows rapid evaluation of one level of efficacy prior to assessing clinical value. Our task is to rouse immunity against weak or tolerizing tumor antigens, and, in order to succeed, we have to build vaccines that contain not only antigen, but also additional essential components. Adjuvants to activate innate immunity are clearly required, and the definition of the Toll-like receptors is opening possibilities for selective stimulation. Delivery of antigen to dendritic cells is a second goal and can be achieved either directly or via gene-based vaccines. Finally, there is a perceived need to activate high levels of T cell help to promote and maintain antibody, CD4+, or CD8+ effector pathways. The easiest way to build components into a vaccine is to use genetic technology, and therefore gene-based vaccines are likely to have a real future. Physical means to improve delivery and potential combinations with viral vector-mediated delivery may be required to optimize performance. Opportunities to codeliver genes encoding cytokines, chemokines, and other molecules are there. It will take time to exploit the new genetic information and technology, and tailoring of vaccines for specific target antigens will be required. Provided flexible and rapid evaluation in pilot clinical trials is allowed at reasonable cost, design will progress to the stage where tumor vaccines will be a reality. Vaccination of patients is litkely to succeed mainly in the setting of minimal residual disease. However, transfer of immunity from vaccinated donors of transplants, or from cells expanded in vitro, should also have a place. Vaccination could enhance the already successful passive immunotherapies being used to attack residual leukemic cells or dangerous viruses in immunosuppressed patients. A successful immune response should provide continuous surveillance against emergent tumor, and this would be a major contribution to the treatment of cancer
Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen
No full textDNA vaccines can activate immunity against tumor Ags expressed as MHC class I-associated peptides. However, priming of CD8+ CTL against weak tumor Ags may require adjuvant molecules. We have used a pathogen-derived sequence from tetanus toxin (fragment C (FrC)) fused to tumor Ag sequences to promote Ab and CD4+ T cell responses. For induction of CD8+ T cell responses, the FrC sequence has been engineered to remove potentially competitive MHC class I-binding epitopes and to improve presentation of tumor epitopes. The colon carcinoma CT26 expresses an endogenous retroviral gene product, gp70, containing a known H2-Ld-restricted epitope (AH1). A DNA vaccine encoding gp70 alone was a poor inducer of CTL, and performance was not significantly improved by fusion of full-length FrC. However, use of a minimized domain of FrC, with the AH1 sequence fused to the 3' position, led to rapid induction of high levels of CTL. IFN-?-producing epitope-specific CTL were detectable ex vivo and these killed CT26 targets in vitro. The single epitope vaccine was more effective than GM-CSF-transfected CT26 tumor cells in inducing an AH1-specific CTL response and equally effective in providing protection against tumor challenge. Levels of AH1-specific CTL in vivo were increased following injection of tumor cells, and CTL expanded in vitro were able to kill CT26 cells in tumor bearers. Pre-existing immunity to tetanus toxoid had no effect on the induction of AH1-specific CTL. These data demonstrate the power of epitope-specific CTL against tumor cells and illustrate a strategy for priming immunity via a dual component DNA vaccine
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
