Adjuvant System AS01 is a liposome-based vaccine adjuvant containing 3-O-desacyl-4′-monophosphoryl lipid A and the saponin QS-21. AS01 has been selected for the clinical development of several candidate vaccines including the RTS,S malaria vaccine and the subunit glycoprotein E varicella zoster vaccine (both currently in phase III). Given the known immunostimulatory properties of MPL and QS-21, the objective of this study was to describe the early immune response parameters after immunization with an AS01-adjuvanted vaccine and to identify relationships with the vaccine-specific adaptive immune response. Cytokine production and innate immune cell recruitment occurred rapidly and transiently at the muscle injection site and draining lymph node postinjection, consistent with the rapid drainage of the vaccine components to the draining lymph node. The induction of Ag-specific Ab and T cell responses was dependent on the Ag being injected at the same time or within 24 h after AS01, suggesting that the early events occurring postinjection were required for these elevated adaptive responses. In the draining lymph node, after 24 h, the numbers of activated and Ag-loaded monocytes and MHCIIhigh dendritic cells were higher after the injection of the AS01-adjuvanted vaccine than after Ag alone. However, only MHCIIhigh dendritic cells appeared efficient at and necessary for direct Ag presentation to T cells. These data suggest that the ability of AS01 to improve adaptive immune responses, as has been demonstrated in clinical trials, is linked to a transient stimulation of the innate immune system leading to the generation of high number of efficient Ag-presenting dendritic cells.

Alum has been the most widely used adjuvant for over 80 years. Although there have been searches for alternative adjuvants, aluminium-containing adjuvants will continue to be used for many years due to their good track record of safety, low cost and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminium-containing adjuvants formulated under optimal conditions are the adjuvants of choice. There are also some limitations of aluminium-containing adjuvants, which include local reactions, augmentation of IgE antibody responses, ineffectiveness for some antigens and inability to augment cell-mediated immune responses, especially cytotoxic T-cell responses. In this review, we describe the current knowledge regarding the mechanisms (both cellular and molecular) by which alum employs its adjuvant effect, although the final mechanism is not yet well-defined. Furthermore, we discuss how alum's adjuvanticity could be improved.

B cells are a major part of the adaptive immune response to inhaled HDM allergen, particularly when the amount of inhaled allergen is low, by expanding allergen-specific T cells.

Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer.

* Neoplasm Recurrence, Local [prevention & control]; Randomized Controlled Trials as Topic; Rectal Neoplasms [ * drug therapy; pathology; * radiotherapy; surgery] 20 Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer (Review)

Mast cells, best known as effector cells in pathogenic immunoglobulin-mediated responses, can sense a variety of “danger” signals; if manipulated to enhance their resulting inflammatory responses, they also exacerbate inflammatory diseases such as arthritis and lung inflammation.

Combining chemotherapy with preoperative radiotherapy (RT) has a sound radiobiological rationale. We performed a systematic review and meta-analysis of trials comparing preoperative RT with preoperative chemoradiation (CRT) in rectal cancer patients. The Cochrane Central Register of Controlled Trials, Web of Science, Embase and Medline (Pubmed) were searched from 1975 until June 2007. Dichotomous parameters were summarized using the odds ratio while time to event data were analyzed using the pooled hazard ratio for death. From the primary search result of 324 trials, 4 relevant randomized trials were identified. The addition of chemotherapy significantly increased grade III and IV acute toxicity (p 5 0.002) while no differences were observed in postoperative morbidity or mortality. Preoperative CRT significantly increased the rate of pathological complete response (p < 0.001) although this did not translate into a higher sphincter preservation rate (p 5 0.29). The local recurrence rate was significantly lower in the CRT group (p < 0.001). No statistically significant differences were observed in disease free survival (p 5 0.89) or overall survival (p 5 0.79). Compared to preoperative RT alone, preoperative CRT improves local control in rectal cancer but is associated with a more pronounced treatment related toxicity. The addition of chemotherapy does not benefit sphincter preservation rate or long-term survival. Future trials should address improvements in the rate of distant metastasis and overall survival by incorporating more active chemotherapy. ' UICCKey words: rectal cancer; radiotherapy; surgery The incidence of fatal cases of colorectal cancer in Europe exceeds 200,000 per year. 1 Because of the specific anatomy and biology of rectal cancer, surgery alone historically has been associated with local recurrence in up to 1 in 4 patients. 2 Locally recurrent disease is usually incurable, causes important morbidity and suffering and gives rise to systemic metastases. In the last few decades, improvements in surgical technique have dramatically lowered the incidence of locally recurrent disease. Careful pathological studies have clearly demonstrated that the major cause of local recurrence is the persistence of tumor foci within the mesorectum. 3,4 Intact removal of the entire mesorectum (total mesorectal excision or TME) in cancers of the mid or lower third of the rectum was pioneered by Heald and has resulted in local recurrence rates lower than 5-10%. [5][6][7] Parallel to improvements in surgical technique, adjuvant therapy regimens have been tested in clinical trials in an effort to reduce local recurrence rates. Neoadjuvant radiotherapy (RT) has been shown to significantly decrease local recurrence rate and improve survival provided a biologically equivalent dose (BED) of at least 30 gray (Gy) is administered. 8 The advantages of preoperative over postoperative RT include enhanced effectiveness in well-oxygenated tissue, downstaging of advanced tumors and better treatment compliance. 9 The theoretical ...

Immune responses can be predicted by the chemical properties of systematically variable inorganic crystalline materials.