BackgroundThere is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC).MethodsThis Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals.ResultsThirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4.ConclusionProduction of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors
This study examined self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their caregivers, and associations between self-efficacy and patient and caregiver adjustment. 152 patients with early stage lung cancer completed measures of self-efficacy, pain, fatigue, quality of life, depression, and anxiety. Their caregivers completed a measure assessing their self-efficacy for helping the patient manage symptoms and measures of psychological distress and caregiver strain. Analyses indicated that, overall, patients and caregivers were relatively low in selfefficacy for managing pain, symptoms, and function, and that there were significant associations between self-efficacy and adjustment. Patients low in self-efficacy reported significantly higher levels of pain, fatigue, lung cancer symptoms, depression, and anxiety, and significantly worse physical and functional well being, as did patients whose caregivers were low in self-efficacy. When patients and caregivers both had low self-efficacy, patients reported higher levels of anxiety and poorer quality of life than when both were high in self-efficacy. There were also significant associations between patient and caregiver self-efficacy and caregiver adjustment, with lower levels of self-efficacy associated with higher levels of caregiver strain and psychological distress. These preliminary findings raise the possibility that patient and caregiver self-efficacy for managing pain, symptoms, and function may be important factors affecting adjustment, and that interventions targeted at increasing self-efficacy may be useful in this population.Self-efficacy, or the confidence in one's ability to perform a specific behavior or task (Bandura, 1997), is one factor that has been examined in relation to patient's adjustment to cancer. Selfefficacy for managing pain, symptoms, and function in particular may be critical to a patient's ability to manage the physical and psychological challenges of cancer. For several reasons, lung cancer provides a particularly good model in which to study self-efficacy for pain and symptom control. First, lung cancer is common, being the second leading site of cancer occurrence among both men and women with over 174,000 new cases projected for 2006 (American Cancer Society, 2006). Second, lung cancer poses significant challenges for patients and their caregivers including aggressive medical treatments and an uncertain prognosis. In Address correspondence to: Laura S. Porter, Ph.D., 2200 West Main St, Suite 340, Durham, NC 27705, USA, email: laura.porter@duke.edu, telephone: 919-416-3436, fax: 919-416-3458.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovere...
This research investigated how voters select, process, are affected by, and recall political information in a dynamic campaign environment. It was hypothesized that voters' information selection, processing, and recall are subject to a negativity bias (i.e., negative information dominates over positive information), a congruency bias (i.e., positive information about the preferred candidate and negative information about the opponent candidate dominate over negative information about the preferred candidate and positive information about the opponent), and a candidate bias (i.e., information about the preferred candidate dominates over information about the opponent). Motivated by an initial candidate preference, participants were also expected to develop more polarized candidate evaluations over time. Participants were exposed to quickly changing information in the form of newspaper-style headlines on a dynamic, computer-based information board. The results generally supported negativity bias and candidate bias, whereas congruency bias was only found during information recall. At the information selection and processing stages, participants with a strong initial candidate preference showed a disproportionate preference for negative information about the preferred candidate. However, they developed more positive attitudes at the evaluation and recall stage. This finding suggests that participants were engaged in motivated information processing by counterarguing negative information about their preferred candidate.
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