Cancer Research - Europa

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Dendritophages Therapeutic cancer vaccines Summary The patient’s blood monocytes are transformed into eff ector monocyte-derived dendritic cells (DC) (dendritophages), which fi ght the patient’s own disease. The therapeutic cell drug comprises dendritic cells, which are loaded with cancer-specifi c antigens to activate the patient’s immune system after re-injection. This project aims to demonstrate the immune and clinical effi cacy, reproducibility and feasibility of anticancer cell vaccine by choosing the best dendritic cell vaccination strategy via adequate pre-clinical studies (DC diff erentiation and maturation, tumour antigens selection and loading, dose delivered, site and vaccination schedule). It will monitor the immune response in correlation to the clinical response after defi ning the most relevant immuno-monitoring techniques, and will demonstrate the immunological effi cacy of DC immunotherapy in prostate cancer, which will be performed after loading ex vivo dendritic cells with proteic antigen. This will require the setting up of quality control criteria and data base design for the production of the cellular product, and optimising a GMP process. We will start a clinical trial to evaluate the cell drug on progressing prostate cancer patients. Problem • Select the most eff ective DC preparation. • Develop GMP process. • Show immunogenicity and safety in carcinoma patients. Aim Keywords | Vaccine dendritic cells | The fi nal goal of anticancer therapeutic vaccines is to prevent metastasis development as well as tumour progression and to provide long-term protection. Previous and ongoing clinical studies have shown that there are no side eff ects associated with this type of dendritic autologous cellular drugs, and that immune and clinical responses can be achieved in some patients resistant to conventional therapies. The preclinical data generated on dendritic cells, as well as pilot clinical trial data, have driven the dendritic cell immunotherapy technology to reach adequate maturity to enter real standardisation and demonstration of immune effi - cacy. A phase I study of anti-tumour immunisation of patients with melanoma stage III or IV has been initiated during a previous EU Project coordinated by the same team, with autologous DCs (BIO-CT97- 2216, CELLULAR VACCINES, 1997). Nine patients had completed the treatment which consisted of four series of injections of dendritic cells pulsed with tumour cell lysate and dendritic cells pulsed with HbsAg and TetanusT. Expected results Results showed excellent safety and the presence of immune responses after vaccination, as well as signs of clinical responses in some of the patients. It is to be noted that one patient showed complete regression of metastases four months after the last vaccination, and another one showed stabilisation of the disease. We have compared several technologies for obtaining DCs and selected the most appropriate for GMP development. The initial clinical results have been confi rmed on a randomised clinical study conducted in malignant melanoma stage IV patients immunised with dendritic cells pulsed ex vivo with three melanoma cell lines lysates. The results of this study are based on 49 treated patients, with 15 patients having completed the cycle of six DC vaccinations, the others progressing due to late stage disease. No severe adverse event has been related to the therapeutic protocol nor to the DC product; the most frequent minor side eff ects were injection site reactions. Fourteen patients out of 49 initiated T-cell immune response against the antigens presented and ten patients had disease stabilisation; most of these immune responses and stabilisations were in the group of patients having received six vaccinations. Studies are ongoing in colorectal and prostate cancer. Potential applications Vaccine therapy of metastatic carcinoma. 186 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Coordinator Jacques Bartholeyns IDM SA Immuno-Designed Molecules Paris, France Partners Andreas Mackensen Dept. of Hematology/Oncology University of Regensburg Regensburg, Germany Miles Prince Centre for Blood Cell Therapies c/o Peter MacCallum Cancer Centre Victoria, Australia TREATMENT Reinhard Glueck Etnabiotech c/o Dipartimento di Farmacologia Sperimentale e Clinica Facoltà di Medicina Università di Catania Catania, Italy Thomas Felzmann Children’s Cancer Research Insitute Kinderspitalgasse Vienna, Austria Filippo Belardelli Istituto Superiore di Sanità Laboratory of Virology Rome, Italy Anne-Cécile de Giacomoni ALMA consulting group Houlbec-Cocherel, France Project number LSHB-CT-2003-503583 EC contribution € 1 999 900 Duration 42 months Starting date 01/04/2004 Instrument STREP Project website www.idm-biotech.com 187
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PROJECT SYNOPSES CANCER RESEARCH PR
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CANCER RESEARCH PROJECTS FUNDED UND
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TABLE OF CONTENTS FOREWORD - CANCER
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Prevention 97 EPIC 98 EUROCADET 100
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CANCER: COMBATING A COMPLEX DISEASE
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Biology Cancer is a disease ethat t
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p53 activators ASPP Partner 5 NFkap
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Keywords | Angiogenesis | vasculoge
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Keywords | Tumour-host interactions
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Keywords | Breast | metastasis | ge
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Keywords | Identifi cation of novel
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Keywords | Systems biology | modell
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Keywords | Oncology | anticancer th
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• public health research coupled
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Expected results We will construct
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Potential applications Our DNA is u
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Microscopic examination of tissue s
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Pluripotent embryonic stem cells ar
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• Decryption of the leukaemia cel
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• identifi cation of molecular ta
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A B C LT-HSC CSC The Cancer Stem Ce
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X-ray diff raction of target drug c
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using pathway-specifi c reporter ce
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Keywords | Kinases | pediatric panc
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Keywords | Lymphangiogenesis | angi
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Keywords | Breast cancer | metastas
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Keywords | Mitosis | phosphorylatio
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Keywords | Therapy | genome | telom
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Keywords | Multiple myeloma | cance
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Keywords | p53 tumour suppressor |
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Development of eff ective anti-canc
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Coordinator Patrick A. Curmi INSERM
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Drosophila as a model system for tu
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Normal cell growth and epithelial l
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effi ciently with cancer cell proli
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A high-throughput assay of transcri
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Coordinator Ewa Sikora Nencki Insti
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Expected results The SIROCCO consor
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Keywords | Epigenetics | gene regul
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Keywords | Hereditary | tricarboxyl
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Keywords | HSV-1 | hepatocellular c
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Keywords | Apoptosis | autophagy |
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Keywords | Tumour | host | signalli
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Aetiology The uncontrolled cell gro
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Coordinator Rosalind Eeles Reader i
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The parallelogram approach in CARCI
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Keywords | Melanoma | genetics | na
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Keywords | Virus | bacteria | HPV |
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Keywords | Breast | prostate | gene
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Prevention The fact that preventing
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Coordinator Elio Riboli Imperial Co
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Coordinator Jan Willem Coebergh Joh
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Coordinator Jose M a Benlloch Conse
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BAMOD Breath-Gas Analysis for Molec
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BioCare Molecular Imaging for Biolo
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These centres of excellence will in
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Expected results Optimise the benef
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114 Cell proliferation and apoptosi
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COBRED Colon and Breast cancer Diag
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DASIM Diagnostic Applications of Sy
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Expected results Primarily, the res
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Coordinator John A. Foekens Dept. o
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124 Aim Drop-Top has two major obje
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Coordinator Gorka Ochoa Progenika B
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Expected results The E.E.T.-Pipelin
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e developed by eTUMOUR is likely to
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Coordinator Angel Porgador Ben-Guri
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• the design of a compact assembl
Page 138 and 139: Potential applications We believe t
Page 140 and 141: Tumor initiation, progression to ma
Page 142 and 143: MolDiag-Paca Novel Molecular Diagno
Page 144 and 145: NEMO Nano based capsule-Endoscopy w
Page 146 and 147: OVCAD Ovarian Cancer - Diagnosis of
Page 148 and 149: P-MARK Validation of recently devel
Page 150 and 151: POC4life Multiparametric quantum do
Page 152 and 153: PROMET Prostate cancer molecular-or
Page 154 and 155: Micrometastasis in the bone marrow.
Page 156 and 157: and pharmaco-kinetics studies. This
Page 158 and 159: Coordinator Raffaella Giavazzi Isti
Page 160 and 161: • Development of tools for diagno
Page 163 and 164: Treatment Two major problems when t
Page 165 and 166: Coordinator Lluis M. Mir UMR 8121 C
Page 167 and 168: Potential applications ANGIOSTOP ha
Page 169 and 170: Green-fl uorescence protein- expres
Page 171 and 172: Coordinator Robert Hawkins Universi
Page 173 and 174: Expected results The BACULOGENES pr
Page 175 and 176: descriptors of the molecules to be
Page 177 and 178: Keywords | Therapeutic vaccine | im
Page 179 and 180: Keywords | Cancer chemotherapy | dr
Page 181 and 182: Keywords | Children | cancer | leuk
Page 183 and 184: Chimaeric TCR shown in context of n
Page 185 and 186: Andrea Splendiani Leaf Bioscience s
Page 187: Coordinator Anne O’Garra The Medi
Page 191 and 192: Structure Driven Drug Design The in
Page 193 and 194: • acquire fundamental knowledge a
Page 195 and 196: Terry Jones Victoria University of
Page 197 and 198: Potential applications The use of t
Page 199 and 200: groups and management structures. T
Page 201 and 202: T. Barbui Azienda Ospedaliera-Osped
Page 203 and 204: Keywords | Mantle cell lymphoma | t
Page 205 and 206: Keywords | Hypoxia | HIF | pericell
Page 207 and 208: Keywords | Radiation-induced compli
Page 209 and 210: Keywords | Gene therapy | adenoviru
Page 211 and 212: Keywords | Dependence receptors | a
Page 213 and 214: Keywords | Photodynamic therapy | a
Page 215 and 216: Keywords | Ovarian cancer | thymidy
Page 217 and 218: Keywords | Quality assurance | clin
Page 219 and 220: Keywords | Circadian | clocks | cel
Page 221 and 222: Keywords | Anticancer therapy | onc
Page 223 and 224: Coordinator Monika Lusky Transgene
Page 225 and 226: 6 000 women over a three-year perio
Page 227 and 228: Keywords | Solid tumours | apoptosi
Page 229 and 230: Keywords | Lymphoma | leukaemia | v
Page 231: Coordinator Riccardo Dolcetti Centr
Page 234 and 235: CCPRB Cancer Control using Populati
Page 236 and 237: EPCRC The European Palliative Care
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EUROCAN+PLUS Feasibility Study for
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EUSTIR A European strategy for the
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NORMOLIFE Development of new therap
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Scientifi c Model Systems The compl
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Performance of benchmarking exercis
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• markers correlating with the im
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Indices - Keywords Indices - Partne
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● disease markers 131 ● DNA dam
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● renal 77 ● replication 219
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Bos, Nico A. 56 Boskovic, Darinka 2
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Geley, Stephan 159 Georgopoulos, Li
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Lingner, Joachim 54 Linial, Michal
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Ragno, Pia 115 Rainford, Martyn 92
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Vernos, Isabelle 22 Veronesi, Umber
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● Centre Hospitalier Universitair
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● IFOM - Fondazione Istituto FIRC
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● National University of Ireland
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● University of Bari 174 ● Univ
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HOW TO OBTAIN EU PUBLICATIONS Our p
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