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

Ensemble pour spectrométrie Môssbauer haute température in situ. Evolution thermique des paramètres Môssbauer de SrFeO2,50

An in situ cell for Môssbauer resonance studies has been described. It allows measurements up to 1100 K with a gas pressure ranging from 1 Pa to 2 x 10^5 Pa. The finely powdered sample is layed on a boron nitride holder. The whole is placed at the center of the reactor. The cell has been used to determine the thermal behavior of SrFeO2.50.Une cellule pour l'étude in situ de la résonance Môssbauer est décrite. Elle est conçue pour des mesures jusqu'à 1100 K dans un domaine de pression gazeuse allant de 1 Pa à 2 x 10^5 Pa. L'échantillon pulvérulent est déposé sur un disque en nitrure de bore. L'ensemble est placé au centre du réacteur. La cellule a été utilisée pour l'étude du comportement thermique de SrFeO2,50

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

The Electrochemical Oxidation : a New Way for Preparing Highly Oxidized Ferrites

The electrochemical oxidation is depicted as a novel and powerful route for preparing highly oxidized ferrites. The reaction is achieved at room temperature, in air, in alkaline solution (1M KOH or NaOH). This process has been used for preparing various new compounds and especially perovskite-type ferrites such as SrMO3 ( M = Fe or/and Co ) or Sr2LaFe3O9-ε. The characterization of the samples shows that they remain well crystallized after the electrochemical treatment and bulky oxidized. The reaction can be described as an intercalation process of oxygen atoms into the host lattice of the starting material. For instance, the chemical analysis as well as Mössbauer spectroscopy data of SrFeO3 or of Sr2FeCoO6 reveal iron cations to be exclusively tetravalent. On the other hand, Sr2LaFe3O9-ε exhibits at decreasing temperature a disproportionation of the mixed valence of iron. Potentiostatic and galvanostatic experiments have shown that the amount of intercalated oxygen can be controlled and that the process is reversible. A mechanism involving the formation of O- species that can diffuse inside the bulk of the material, is proposed

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

Détermination structurale des fluorozirconates de thallium trivalent

International audienc

Spectroscopic and magnetic properties of alpha-Li3Fe2(PO4)(3): A two-sublattice ferrimagnet

Spectroscopic and magnetic studies on alpha-Li3Fe2(PO4)(3) show an interesting behavior blow the transition temperature (29 K). The compound orders antiferromagnetically, presenting a weak ferromagnetic moment, which diminishes with temperature. In the same-region of temperatures, the Mossbauer spectra split; in two sextets with slightly different hyperfine fields, and the ESR spectrum reduces its intensity and broadens. These results are interpreted as the competition between two sublattices of Fe(III) ions, corresponding to the presence of two independent Fe(III) crystallographic sites in the structure. The magnetic interaction in each sublattice is ferromagnetic, being coupled antiferromagnetically between them. The observed weak ferromagnetic component is the result of the ferrimagnetic character in the coupling between two Fe(III) sublattices.121626

The impact of gallic acid on iron gall ink corrosion

Many old manuscripts suffer from iron-gall ink corrosion, threatening our graphic heritage. Corroded papers become brown and brittle with age.