Evaluation of in vivo labelled dendritic cell migration in cancer patients

BACKGROUND: Dendritic Cell (DC) vaccination is a very promising therapeutic strategy in cancer patients. The immunizing ability of DC is critically influenced by their migration activity to lymphatic tissues, where they have the task of priming naïve T-cells. In the present study in vivo DC migration was investigated within the context of a clinical trial of antitumor vaccination. In particular, we compared the migration activity of mature Dendritic Cells (mDC) with that of immature Dendritic Cells (iDC) and also assessed intradermal versus subcutaneous administration. METHODS: DC were labelled with (99m)Tc-HMPAO or (111)In-Oxine, and the presence of labelled DC in regional lymph nodes was evaluated at pre-set times up to a maximum of 72 h after inoculation. Determinations were carried out in 8 patients (7 melanoma and 1 renal cell carcinoma). RESULTS: It was verified that intradermal administration resulted in about a threefold higher migration to lymph nodes than subcutaneous administration, while mDC showed, on average, a six-to eightfold higher migration than iDC. The first DC were detected in lymph nodes 20–60 min after inoculation and the maximum concentration was reached after 48–72 h. CONCLUSIONS: These data obtained in vivo provide preliminary basic information on DC with respect to their antitumor immunization activity. Further research is needed to optimize the therapeutic potential of vaccination with DC

Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy

The Messina Strait Bridge: A Challenge and a Dream

This book describes the enormous depth of work carried out since the early seventies on the Messina Strait Bridge, up to the recent award of the detailed design and construction contract. This important work has included extensive studies, concepts and design developments, with far reaching applications, which have all confirmed the feasibility of this huge endeavour and have led to the optimisation of costs and expected performance levels. Attention is focused not only on the design itself, but also on the context for the project (e.g. historical, geological, seismo-tectonic and wind conditions; structural and mechanical properties; project management and financial aspects; and environmental considerations), and on the great challenges involved. Thus, considering the innovations and specific solutions adopted in overcoming the challenges presented by constructing a world record span of 3,300 metres at this site, it becomes clear how the Messina Strait Crossing will take its place as a masterpiece in bridge engineering history. This book will be of interest to bridge and structural engineers, geotechnical and wind engineers, mechanical and earthquake engineers, graduate students in all these areas and all others with a broad interest in bridge design and engineering

Apollo. A. 5(Gennaio 1965 - Dicembre 1984)

A. 5(gen.1965 - dic.1984): De Franciscis, A., Presentazione, P. 5 ; Panebianco, V., Ricordo di Antonio Marzullo, P. 7 ; Marzullo, B., Ricordo di Padre: Antonio Marzullo, P. 9 ; Gigante, M., Ricordo di Venturino Panebianco, P. 15 ; Nabers, N., A new hydria by the Pan Painter, P. 31 ; Trendall, A. D., A red-figured calyx-krater from Nocera, P. 47 ; Varone, A., Un miliario del Museo dell’Agro Nocerino e la via di Nocera al porto di Stabia (e al capo Ateneo), P. 59 ; Avagliano, G., Fratte di Salerno. Tomba VI/1971, P. 87 ; Fabbri, B., Guarino, D. P., e R. Maldera, Caratterizzazione tecnologica di un corredo ceramico della necropoli di Fratte, P. 95 ; Bignardi, M., Un ignoto salernitano della prima metà del quattrocento (l’affresco del vicolo dei Sediari), P. 127 ; Migliorini, P. M., La Certosa di Padula nella prima metà del ‘700 e le sue immagini, P. 133 ; D’Aniello, A., Contributo per la ricostruzione del disperso patrimonio della Certosa di S. Lorenzo diPadula, P. 145 ; Tamajo Contarini, M., Contributo alla conoscenza del patrimonio artistico della Certosa di Padula: il solimeniano Alessio D’Elia, P. 153 ; Samaritani, C., L’attività dei Musei Provinciali del Salernitano dal 1965 al 1984. P.165 ; Cipriani, M., Il Museo Archeologico Provinciale di Salerno, P. 183 ; Mangieri, G. L., Nota sulla Collezione Numismatica del Museo Archeologico Provinciale di S. Benedetto in Salerno, P. 187 ; Avagliano, G., La zona archeologica di Fratte, P. 191 ; Fiammenghi, C. A., Il Museo archeologico della Lucania Occidentale nella Certosa di Padula, P. 199 ; Varone, A., Il Museo dell’Agro Nocerino, P. 205 ; Iannelli, M. A., Il Museo della Ceramica Vietrese, P. 207 ; D’Andria, R., La sezione “Guido Gambone”: priorità di un’iniziativa, P. 215 ; Iacoe, A., La ceramica del Castello di Salerno, P. 221 ; Di Santo, A., Antiquarium di Sala Consilina, P. 223 ; Rota, L., Antiquarium di S. Marzano, P. 225 ; Falanga, L. Recenti contributi alla conoscenza di Salerno romana, P. 227 ; Compagnone, A., Profili storico della ceramica di Vietri, P. 249

Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

BACKGROUND: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. METHODS: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or – homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC) (range 4.5 – 82 × 10(6)) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2–26 × 10(6)). Subcutaneous interleukin-2 (3 × 10(6 )IU) was administered from days 3 to 7 of each treatment cycle. RESULTS: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SD (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 – 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3–14) for the 11 DTH-negative patients (P < 0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). CONCLUSION: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival