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Vaccination Journals

Survivin appears to function mainly as an anti-apoptotic molecule and its ability to interfere with p53 is one of its most studied molecular action. However, the presence of survivin in the nucleus; its interaction with the mitotic spindle; its secondary localization inside mitochondria; its presence in exosomes in plasma observed exosomal release; and the existence of circulating survivin-encoding mRNA; and the existence of a many alternative mRNA splice variants all paint a complex picture of the molecule’s possible actions. Although expressed during fetal development. Due to its relatively specific expression in cancer cells, survivin presents a therapeutic target. Immunotherapy by active immunization is one promising means by which survivin-expressing cancer cells can be targeted. Vaccines directed against an intracellular protein, such as survivin, target the post-proteasomal processed, fragments of the molecule which are presented at the cell surface by MHC class I or class II molecules. While the action of exosomalsurvivin is not well understood, it may mediate cellular signaling in some way. Thus, in addition to producing a direct cell-mediated antitumor effect, active specific vaccination against survivin could lead to antibody-mediated interference with these actions. A number of anti-tumor vaccine strategies have used cell-surface target molecules like HER2/neu, EGFR and EGFRvIII which are accessible to both cellular and antibody-mediated immune attack. A number of survivin-targeting immunotherapeutic strategies have been developed to date. Dendritic cell (DC)-based vaccines are attractive due to the tremendous antigen presentation potential of DC. Dendritic cell vaccines pulsed with apoptotic bodies of cells that over-expressed survivin (as well as Her2, CEA, WT1 and MAGE2) have been studied in non-small cell lung cancer (NSCLC). This study showed positive immune responses in 10 of 14 patients, along with anecdotal clinical responses. Several survivin peptide vaccines are also currently under development. Most recently, this peptide vaccine has shown promise in metastatic urothelial cancer where 30 patients had significantly better overall survival compared to controls. This particular vaccine utilizes a very specific epitope that is not present in all survivin forms. Immunotherapy targeting survivin is still at an early stage of development; however, several agents are rapidly moving through phase I and phase II clinical trials. Recent studies demonstrate that the toxicity profile of this mode of vaccine therapy is good and that significant immune responses can be generated with some clinical responses apparent as well.(Michael J Ciesielski, JingxinQiu and Robert A Fenstermaker, Survivin as a Cancer Vaccine Target)
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Last date updated on July, 2014

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