Rise and Fall of an Anti-MUC1 Specific Antibody

So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10) M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology

The FtsK Family of DNA Translocases Finds the Ends of Circles.

International audienc

Resolution of Multimeric Forms of Circular Plasmids and Chromosomes.

International audienc

SODIUM IRON FLUOROPHOSPHITE GLASSES PART II. EPR AND MÖSSBAUER RESONANCE STUDY

EPR and Mössbauer measurements have been performed on sodium iron fluorophosphate glasses. Mössbauer spectra show the presence of Fe3+ and Fe2+ both in octahedral coordination sites. However, for low iron concentration, EPR suggests a small number of Fe3+ tetrahedra coexisting with Fe3+ octahedra. On the basis of these results, Fe3+ tetrahedrally and/or octahedrally coordinated, connected with P(O,F)4 tetrahedra would behave as a network-former cation, whereas Fe2+ would substitute for Na+ as a network-modifier. Long range magnetic order previously observed by magnetic measurements has been confirmed for iron-rich compositions

Etude magnétique et par résonance Mössbauer de l'orthophosphate Na 3Fe2(PO4)3α et d'une phase vitreuse dérivée

A study of Na3Fe2(PO4)3α by magnetic susceptibility measurements and Môssbauer spectroscopy has shown antiferromagnetic ordering at 45.7 K with some weak ferromagnetism. A vitreous phase has been formed by quenching the molten material. The presence of both divalent and trivalent iron was detected. It has been established that this reduction of iron was necessary to the vitrification process. The magnetic structure of the glass has been discussed.L'étude magnétique et par résonance Mössbauer de Na3Fe 2(PO4)3α a permis de mettre en évidence un ordre antiferromagnétique à 45,7 K accompagné d'un faible ferromagnétisme. Une trempe après fusion conduit à une phase vitreuse. Son étude indique la présence simultanée de fer divalent et trivalent. Il a été établi que cette réduction du fer était indispensable pour que se produise le processus de vitrification. La structure magnétique du verre est discutée