Preparing Europe for a new renaissance: how science can help restore sustainable prosperity.

On 6 October 2009, ERAB (European Research Area Board) presented its first annual report "Preparing Europe for a New Renaissance--A Strategic View of the European Research Area". As a vision paper it paints a picture, in broad strokes, of where the European Research Area (ERA) needs to go by 2030--for the sake of the European Union, and of the world at large. For this purpose, the ERAB Conference entitled "Preparing Europe for a new Renaissance" was held on May 6-7, 2010, in Seville, Spain. The aim of the ERAB Conference was to discuss widely with public and private stakeholders the implementation of the Strategic view on European Research Area. The Commissioner Máire Geoghegan-Quinn deserves a special mention since set a challenge to the ERAB Conference in her speech. Thus, she asked the conference to provide her with ten concrete proposals on how research, innovation and science can contribute to addressing society's grand challenges, to prepare Europe's post-crisis smart, green economy and society. The ERAB welcomed the challenge. Based on the feedback from the conference delegates and own discussions the ERAB came up with 10 key recommendations. Below we reproduce a speech by the European Commissioner for Research, Innovation and Science, Máire Geoghegan-Quinn given at the ERAB Conference.

Binding to CD20 by anti-B1 antibody or F(ab')(2) is sufficient for induction of apoptosis in B-cell lines.

CD20 is a B-cell-specific cell surface protein expressed on mature B lymphocytes and is a target for monoclonal antibody therapy for non-Hodgkin's lymphoma (NHL). Though clear clinical efficacy has been demonstrated with several anti-CD20 antibodies, the mechanisms by which the antibodies activate CD20 and kill cells remain unclear. Proposed mechanisms of action include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and induction of apoptosis. In this report we compared the activity of two anti-CD20 antibodies, Anti-B1 Antibody (tositumomab) and rituximab (C2B8), in a variety of cellular assays using a panel of B-cell lines. Anti-B1 Antibody showed a low level of activity in a CDC assay against complement-sensitive B-cell lines, Ramos and Daudi. We found that there is an inverse correlation between the expression of CD55 and CD59 and CDC mediated by either Anti-B1 Antibody or rituximab. Rituximab was more potent at inducing CDC when compared to Anti-B1 Antibody. Using Raji cells as target cells and human peripheral blood leukocytes as effector cells, Anti-B1 Antibody was a potent inducer of ADCC. The activities of Anti-B1 Antibody and rituximab were nearly identical in the ADCC assay. In addition, Anti-B1 Antibody showed direct induction of apoptosis in all B-cell lines tested. In general, crosslinking Anti-B1 Antibody with a goat anti-mouse Ig did not further enhance the percentage of cells undergoing apoptosis. Importantly, a F(ab')(2) fragment of Anti-B1 Antibody induced apoptosis, while the Fab fragment did not, indicating that the Fc region was not required and dimerization of CD20 may be sufficient for induction of apoptosis. In contrast, rituximab, which binds to an overlapping epitope on CD20 with a three-fold lower affinity than Anti-B1 Antibody, did not efficiently induce apoptosis in the cell lines tested in the absence of crosslinking. In conclusion, these two anti-CD20 antibodies have overlapping, but distinct mechanisms of action on B-cell lines.