CNB-CSIC (Coordinator)

Centro Nacional Biotecnología - Madrid

Dr. Luis Ángel Fernández Herrero is Group leader (Científico Titular) of the Antibody Selection and Production Group at the Centro Nacional de Biotecnología (CSIC). For the past eight years, the experimental focused on the development of novel E. coli expression systems to express both scFv and VHH antibodies in either the cytoplasm, the periplasm or the bacterial surface.

These results have been published articles in the top-cited journals in the filed. The group has developed protocols for the construction and selection of phage-antibody libraries from immunized mice and camels. The CNB has excellent laboratory facilities to support the project.

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Hospital Universitario Puerta de Hierro

Dr. Laura Sanz Alcober, Head of the Molecular Immunology Unit at Hospital Universitario Puerta de Hierro, has focused her scientific career on the study of tumor angiogenesis and its inhibition as a therapeutic strategy, reflected in: a) development of antiangiogenic reagents with antitumoral effect in vivo, taking advantage of the accumulated expertise in selection of human antibody fragments using repertoires displayed on filamentous bacteriophages and antibody engineering; b) establishment of in vivo models of human vasculature in immunodeficient mice based on tissue engineering and molecular imaging techniques or primary tumor xenografts, for monitorization of responses to antiangiogenic agents; c) development of high-throughput screening systems for the screening of candidates with potential antiangiogenic effect. Another research line has used gene therapy strategies for cancer treatment, and several works have shown the in vivo secretion of recombinant antibodies by ex vivo gene-modified human cells. Recently, a new research line has been open to address the complex tumor-stroma-immune system interactions, with special focus on the vascular compartment.

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Centro Nacional de Investigaciones Oncológicas (CNIO)

Dr. Jorge Luis Martínez Torrecuadrada has more than fifteen years of experience in Biotechnology research and has participated in many national and international projects. Four years ago, he moved as Staff Scientist to the Protein Technology Unit of the Spanish National Cancer Centre (CNIO) which is headed by Dr. Ignacio Casal. The research group has developed during this time an ample experience in phage display technology, including the cloning of repertoires of several hybridomas, selection, identification and expression of specific scFvs against numerous proteins of interest in cancer research. Also, the functional and biochemical characterizations of several scFvs have been carried out by surface plasmon resonance (BIACORE), flow cytometry (FACS), immunohistochemistry, confocal microscopy and production of mice bearing xenografts (25). Recently, an Imaging Unit has been created at the CNIO with the most modern techniques of in vivo imaging (PET) that will actively collaborate in the diagnosis by imaging of the angiogenic processes using the selected rAbs.

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Universidad Autónoma de Madrid (UAM)

Dr. Antonio Rodríguez Márquez, Research Scientist (“Ramon y Cajal” Programme) of the Molecular Biology Department of the Autonomous University of Madrid, has fifteen years of experience in Molecular Biology and in the last 5 years, he has specifically worked on the molecular basis of angiogenesis within the laboratory of Dr. Juan Miguel Redondo (CBMSO/CNIC) allowing him to obtain a wide experience in techniques of in vitro angiogenesis (capillary tubes formation in Matrigel, invasion in collagen gels, endothelial migration in transwell) and in vivo (corneal neovascularization assay, implantation of Matrigel subcutaneously and tumoral implantation by xenografts). On the other hand, his group is currently using several techniques for the purification of proteins involved in angiogenesis. In addition, in the last 2 years, Dr. Rodríguez has carried out his work in the Autonomous University of Madrid as well as in the Spanish National Center for Cardiovascular Research (CNIC), a centre of new creation with the most modern technology.

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Centro Nacional de Investigaciones Cardiovasculares (CNIC)

La Dra. Alicia G. Arroyo, Investigador Senior/Associate Professor del Departamento de Biología Vascular e Inflamación del Centro Nacional de investigaciones Cardiovasculares de Madrid, posee 25 años de experiencia investigadora en Biología Celular durante los cuales ha investigado distintos aspectos de los procesos celulares implicados en la respuesta angiogénica tales como la regulación de la adhesión de células endoteliales a través de integrinas beta1. Desde su establecimiento como grupo independiente en 1999, sus intereses científicos se han centrado en analizar los componentes celulares y moleculares involucrados en la formación de nuevos capilares en respuesta a factores inflamatorios. Se ha identificado en este sentido la proteasa de matriz MT1-MMP como una molécula clave en la respuesta angiogénica a diversos factores inflamatorios y por tanto como una posible diana terapéutica en enfermedades inflamatorias crónicas que cursan con un fuerte componente vascular (artritis reumatoide, aterosclerosis, psoriasis, etc). En el laboratorio se tiene amplia experiencia en cultivos primarios de células endoteliales de ratón y humanas, en técnicas de angiogénesis in vitro (formación de túbulos en Matrigel, invasión en geles de colágeno, migración endotelial en transwell) e in vivo (vascularización de retina en ratones neonatos, implantación de Matrigel subcutáneo) así como en modelos animales de enfermedades inflamatorias crónicas que cursan con hipervascularización. Más recientemente se han realizado análisis proteómicos y genómicos en células endoteliales activadas por agentes inflamatorios y se ha adquirido experiencia en análisis bioinformático de rutas y procesos biológicos. Además se está adquiriendo experiencia en técnicas de microscopía confocal avanzada y software de análisis de imagen. El grupo se incorporó en 2003 al Centro Nacional de Investigaciones Cardiovasculares (CNIC), centro de nueva creación dotado de la más moderna tecnología y referente en la investigación básica y traslacional de enfermedades cardiovasculares.

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Associated Company

Lead Artis

Lead Artis (www.leadartis.com, Madrid) is a biotechnology company dedicated to the research and development of recombinant antibodies based on proprietary technology (Trimerbody®) which allows the generation of multivalent and multispecific antibodies with optimized configurations by utilizing the trimerization domain of collagen and a flexible peptide linker. The Trimerbody format, besides multispecificity and mutivalency, offers additional advantages over conventional antibodies including smaller sizes, higher avidity for the therapeutic targets, pharmacokinetics adapted to different disease settings and different effector functions. LeadArtis and the Trimerbody platform cover a wide range of development areas being our priorities cancer immunotherapy and inhibition of pathological angiogenic processes.

Associated Company

PROALT (Protein Alternatives SL)

PROALT (www.proteinalternatives.com/) PROALT (Protein Alternatives SL), PROALT (Protein Alternatives SL) is a biotechnology company founded in 2006, located in the Science Park of Madrid, with a strong expertise in those technologies required for the production of recombinant proteins and antibodies. Our focus is to become a reference company developing cancer biomarkers because their critical role in early diagnostic, prognostic and prediction of resistance or drug susceptibility in cancer treatments.
Our aim is to offer quality reagents for the new genomic and proteomic targets arising from the -omics technologies.
PROALT is applying its know-how, strong experience and innovative technologies for the expression, purification and antibody generation of "rare" and "difficult-to-express" proteins to provide high quality products and tailored customer services to the scientific community.

Associated Company

Bacmine (Molecules for Life)

www.bacmine.com

External Advisors

Dr. Serge Muyldermans is Research Professor at the Flemish Free University of Brussels (VUB, Belgium) and one of the most prestigious international experts in the field of recombinant antibodies. Participated in the discovery of camelid antibodies devoid of light chains and has been the main player for its development of biotechnology as VHH fragments. He is also founder and chief scientist of the company 'Ablynx' www.ablynx.com dedicated to the identification of therapeutic VHH(Nanobodies).

 

Dr. Kari Alitalo is Research Professor of Molecular Cancer Biology Program, University of Helsinki. One of the most prestigious international experts in the field of angiogenesis, having made significant contributions to the discovery of tyrosine kinase receptors and their ligands involved in the process, such as FGFR-4, VEGFR-1, NP-1 and VEGF -B.

 

Dr. Oriol Casanovas is Group Leader at the Catalan Institute of Oncology IDIBELL. His work in recent years has focused on the mechanisms that determine the emergence of resistance to antiangiogenic therapy and the effect on tumor progression of these therapies. It was one of the first to warn about the potential effect of inhibitors of VEGF in increasing tumor invasiveness and metastasis formation, with obvious implications for therapies that are common in the clinic.

 

Dr. James Piulats was Director of the Bioresearch Laboratory (LBI) of the German Pharmaceutical company Merck (www.merck.es) at Barcelona until 2008. In collaboration with the Cancer Research Center in Darmstadt (Germany) and Lexigen (U.S.) collaborated decisively in the development of cetuximab (Erbitux ®), a chimeric MAb that recognizes the human EGFR. Currently working as a teacher and consultant to universities and biotech companies.

 

Dr. Carlos Gutierrez is Professor of Department of Animal Pathology, University of Las Palmas de Gran Canaria. He has developed his professional career in the field of internal medicine ruminants and camelids, animal trypanosomosis being one of its main lines of research. More recently he has started several collaborations with research groups of CNB-CSIC, Madrid and Brussels VUB-generating Nanobodies or camelid VHH.