Cancer Research - Europa

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Grid Based IT Support for Drug Discovery. Coordinator István Bágyi AMRI Hungary Hungary research and development INC Budapest, Hungary istván.bágyi@amriglobal.com Partners Mart Saarma University of Helsinki Helsinki, Finland Balazs Borsi GKI Economic Research Co Budapest, Hungary Peter Kacsuk Computer and Automation Research Institute Hungarian Academy of Sciences Budapest, Hungary 174 Amiram Goldblum University of Jerusalem Jerusalem, Israel Saverio Minucci DAC s.r.l. Milano, Italy Angelo Carotti University of Bari Bari, Italy Ferran Sanz University Pompeu Fabra Barcelona, Spain Sándor Cseh TargetEx Budapest, Hungary Project number LSHC-CT-2006-037559 EC contribution € 2 804 075 Duration 36 months Starting date 01/01/2007 Instrument STREP – SME Project website www.cancergrid.eu CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Therapeutic vaccine | immunomonitoring | DC | CTL | CD4 | Treg | melanoma | tumour escape | Ag processing | CANCERIMMUNOTHERAPY Cancer immunology and immunotherapy Summary The first part of the project consists of clinical trials of vaccination, to compare various vaccines, such as peptides and RNA, with diff erent types of immunological adjuvants and dendritic cells. Safety and clinical efficacy will be the primary endpoints of these trials. A large eff ort will be devoted to monitoring the anti-vaccine T-cell responses, as examining the correlation between immunological and clinical responses to the vaccines will be crucial to understanding which factor(s) limit tumour regression. A second part of the project,tightly connected to the clinical trials as it uses biological material from the vaccinated patients, consists of optimising tumour vaccines and combating immune evasion. Foreseeable mechanisms of tumour escape will be analysed and correlated with the clinical results. Improved modalities of vaccination will be tested and new target antigens will be identified. All these results will help to design improved vaccines. Finally, considering the complexity of mechanisms that may lead to or prevent tumour regression in vaccinated patients, we propose to explore more fundamental aspects of the anti-tumour immune response. This includes the cross-presentation of tumour antigens by dendritic cells, recruitment of cells of the innate immune system, involvement of suppressor T-cells, and development of murine models of inducible tumours. If new concepts emerge from this work, they will also help in the design of better vaccines. Problem Cancer is a major life-threatening disease and the second greatest cause of mortality in Europe after cardio-vascular diseases. Classical cancer treatment still relies on surgery, chemotherapy and radiotherapy. Despite clear progress in some cancer types, cancer therapy in general often fails to prevent disease progression to metastatic disease. In addition, these approaches are by themselves very toxic, imposing a heavy burden of side eff ects on the patient. There is clearly a need for new therapeutic approaches that would be more efficient and less toxic. TREATMENT Aim The ultimate objective of this Integrated Project is to develop a therapeutic cancer vaccine with defined tumour antigens that would provide a clinical benefit in at least 40 % of patients. This threshold of 40 % of vaccinated patients showing an objective tumour response, in the absence of unacceptable toxicity, would definitely qualify immunotherapy as a standard cancer treatment. Further improvements could come from refining the vaccinations, and from combining tumour vaccines with other modalities of cancer treatment. Expected results We believe that the principal objective of our project is reachable, for the following reasons: • the preliminary observation that vaccination with tumour antigens can be associated with tumour regressions, and in a few cases with sustained remissions, is encouraging, as it indicates that the vaccines tested so far have an anti-tumoural activity. Considering that vaccineinduced immune responses and tumour regressions seem to be correlated, and that the immune responses that have been detected so far appear to be quantitatively weak, it is reasonable to hypothesise that vaccines with a greater immunogenicity, such as those we plan to investigate, will also have a greater clinical efficacy; • our project will build a close interaction between the research laboratory and the clinic, which allows new ideas emerging from observations made in either of these two fields to be integrated rapidly into new projects; • our consortium comprises groups with an excellent record in clinical trials, T-cell immunology, dendritic cell biology, and mechanisms of tumour resistance. Many of these groups have a longstanding experience of collaborative programmes with each other, both in the laboratory and the clinical trial fields. Potential applications Development and validation of surrogate end-points is a high priority in cancer vaccine research. The project will contribute to this goal by promoting standardised assays and methods for the immunomonitoring of clinical trials. In practice, validation of these surrogate markers may prove extremely useful for meaningful comparisons of various immunisation modalities and as markers of consistency for a given product. 175
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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
Page 126 and 127: 124 Aim Drop-Top has two major obje
Page 128 and 129: Coordinator Gorka Ochoa Progenika B
Page 130 and 131: Expected results The E.E.T.-Pipelin
Page 132 and 133: e developed by eTUMOUR is likely to
Page 134 and 135: Coordinator Angel Porgador Ben-Guri
Page 136 and 137: • 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: descriptors of the molecules to be
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 and 188: Coordinator Anne O’Garra The Medi
Page 189 and 190: Coordinator Jacques Bartholeyns IDM
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
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Keywords | Solid tumours | apoptosi
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Keywords | Lymphoma | leukaemia | v
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Coordinator Riccardo Dolcetti Centr
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CCPRB Cancer Control using Populati
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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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