O Ob bj je ec ct ti iv ve e The primary aim was to evaluate the validity of a teledentistry system for screening new patient orthodontic referrals. The secondary aims were to evaluate whether the teledentistry system affected i) referral rates ii) inappropriate referral rates iii) number of failed appointments. S St tu ud dy y d de es si ig gn n Randomised controlled trial. S Sa am mp pl le e Fifteen dental practices in Greater Manchester, UK, were randomly allocated to either a teledentistry test group (n = 8) or a control group (n = 7). They referred 327 patients over a 15 month period. M Me et th ho od d Practitioners in the test group referred patients to one of two consultant orthodontists via a 'store and forward' teledentistry system consisting of photographs sent as email attachments. The decision to accept or not accept a referral on this basis was compared with the same decision choice when the same patient was subsequently seen on a new patient clinic. This measured the validity of the system with the clinic's decision used as the gold standard. Patients in the control group were referred using the usual letter system. Referral rates, inappropriate referrals and number of failed appointments were then compared between the teledentistry and control groups. R Re es su ul lt ts s The sensitivity (true positive value) of the teledentistry system was high at 0.80 with a positive predictive value of 0.92. The specificity (true negative value) was slightly lower at 0.73 with a negative predictive value of 0.50. The inappropriate referral rate for the teledentistry group was 8.2% and for the controls 26.2% (p = 0.037). There was no statistically significant difference in clinic attendance between teledentistry and control groups (p = 0.36). C Co on nc cl lu us si io on ns s Teledentistry is a valid system for positively identifying appropriate new patient orthodontic referrals. However, there is a risk that a patient is not accepted on the teledentistry system who would benefit from a full clinical examination. Teledentistry could be a significant factor in reducing the inappropriate referral rate. Patient participation in a teledentistry system does not appear to mean they are any more likely to attend their hospital appointment.

No abstract

The role of B cells in T-cell priming is unclear, and the effects of B-cell depletion on immune responses to cancer vaccines are unknown. Although results from some mouse models suggest that B cells may inhibit induction of T cell-dependent immunity by competing with antigen-presenting cells for antigens, skewing T helper response toward a T helper 2 profile and/or inducing T-cell tolerance, results from others suggest that B cells are necessary for priming as well as generation of T-cell memory. We assessed immune responses to a well-characterized idiotype vaccine in individuals with severe B-cell depletion but normal T cells after CD20-specific antibody-based chemotherapy of mantle cell lymphoma in first remission. Humoral antigen- and tumor-specific responses were detectable but delayed, and they correlated with peripheral blood B-cell recovery. In contrast, vigorous CD4(+) and CD8(+) antitumor type I T-cell cytokine responses were induced in most individuals in the absence of circulating B cells. Analysis of relapsing tumors showed no mutations or change in expression of target antigen to explain escape from therapy. These results show that severe B-cell depletion does not impair T-cell priming in humans. Based on these results, it is justifiable to administer vaccines in the setting of B-cell depletion; however, vaccine boosts after B-cell recovery may be necessary for optimal humoral responses.

Nonimmunogenic antigens can be efficiently rendered immunogenic by targeting them to antigen-presenting cells via differentially expressed chemokine receptors. For example, self-tumor or HIV antigens genetically fused with proinflammatory chemoattractants elicit potent immune responses and protective antitumor immunity in mice. Herein we demonstrate that the mechanism by which chemokine fusions elicit responses is efficient uptake, processing, and presentation of antigens via the major histocompatibility complex class II pathway. Experiments with inhibitors of intracellular trafficking suggest that chemoattractant fusion proteins, but not antigen alone, were processed and presented through early/late endosomal and Golgi compartments and stimulated antigen-specific CD4 ؉ T cells both in vitro and in vivo. IntroductionCell trafficking is regulated by differential expression of heterotrimeric Gi protein coupled 7-transmembrane-domain chemokine receptors (GPCRs). 1 Sentinel antigen-presenting cells (APCs), the immature dendritic cells (DCs), preferentially express CCR1, CCR2, CCR5, and CCR6. [2][3][4] Upon ligand binding the receptor is phosphorylated and endocytosed through clathrin-coated vesicles using ␤-arrestin adaptors, [5][6][7] although some viral chemokine receptors, such as US28, are endocytosed independently of ␤-arrestins. 8 The internalized receptors may then be dephosphorylated and recycled back to the cell surface or targeted for degradation. 5,9 CCR5 is transported to early endosomes and subsequently recycled to the cell surface, bypassing the Golgi apparatus and late endosomes, and this process does not involve protein synthesis. 5 Upon chemokine receptor binding, the chemokine ligand is also internalized although its fate is not known and presumed to be degraded. Moreover, the fate of the internalized receptor and the bound ligand may be regulated by the strength of the ligandinduced signaling or the nature of the ligand itself. For example, CCR5 is endocytosed through clathrin-coated vesicles on binding to RANTES or AOP-RANTES (aminooxypentane regulated-onactivation normal T-expressed and secreted), although the latter drives CCR5 to a degradation pathway, whereas RANTES-bound CCR5 is recycled to the cell surface. 5,10 The internalized receptors are degraded by proteosomes, which are considered as major regulators of cytokine receptor expression. [11][12][13] Active immunotherapy based on the targeting of idiotypic antigen (Id), expressed by malignant B cells, is one of the most promising human cancer vaccine approaches. 14 Recently, we have demonstrated that effective adaptive immunity against weakly immunogenic tumor antigens could be induced by targeted delivery of such antigens to chemokine receptors on professional APCs by linkage to their chemoattractant ligands (␤-defensins or chemokines). Mice immunized with chemoattractants fused with nonimmunogenic lymphoma Id or sFv elicited potent anti-idiotypic responses and were protected from challenge with a lethal dose of syngeneic lymphoma cells...

Purpose: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrierconjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients.Experimental Design: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses.Results: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4 ؉ and CD8 ؉ T cells, were human lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission.Conclusions: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4؉ and CD8 ؉ T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.