Anticorps humanisés en thérapeutique

En 2002, il était prévu que les anticorps humanisés deviendraient une classe majeure de médicaments, notamment en cancérologie. Aujourd’hui, huit d’entre eux sont utilisés en clinique et plus de quarante font l’objet d’essais cliniques. Si leurs mécanismes d’action, multiples, sont difficiles à préciser pour un anticorps donné, les observations réalisées chez les milliers de patients déjà traités démontrent clairement leur intérêt clinique. Ils sont cependant d’utilisation délicate, en particulier lorsqu’ils modulent l’activité d’effecteurs de la réponse immune. Au cours des prochaines années, de nouveaux progrès devront être faits pour sélectionner les cibles pertinentes de ces anticorps, diminuer leur immunogénicité et réduire leur coût.Since 1997, nine humanized antibodies received the approval of the FDA to be used as drugs for the treatment of various diseases including transplant rejections, metastatic breast and colon cancers, leukaemia, non-Hodgkin lymphomas, allergic conditions or multiple sclerosis. This review describes techniques used to engineer these antibodies and presents the recent evolutions of these techniques : SDRs grafting or « abbreviated » CDRs grafting. Based on the illustrative examples of several antibodies, Mylotarg®, Herceptin® or Xolair®, the therapeutic effectiveness of humanized antibodies are underlined and, with the example of Tysabri®, the sometimes dramatic adverse effects associated with their clinical use is stressed. In a second part, this review presents some future and realistic avenues to improve the effectiveness of the humanized antibodies, to decrease their immunogenicity and to reduce their cost

A Two-Site Immunoradiometric Assay for Serum Calcitonin Using Monoclonal Anti-Peptide Antibodies

We have produced a library of monoclonal antibodies of various affinities by immunizing mice with synthetic calcitonin (CT) 1-32. These monoclonal antibodies defined two antigenic determinants on the molecule of CT. The first was located in the 11-17 region of the hormone: the second was present on the 26-32 portion of CT. The C-terminal epitope was restricted to the mature form of the hormone and immunologically silent on synthetic peptides with sequences analogous lo the biosynthetic precursors for CT. Using two high-affinity monoclonal antibodies, designated as CT07 and CT08, we developed a two-site immunoradiometric assay (m-lRMA) for serum CT. This m-lRMA provided a sensitivity of 10 pg/mL using a one-step overnight incubation at room temperature. Gel filtration analyses of serum samples from patients with medullary thyroid carcinoma (MTC) demonstrated that the CT07-CT08 m-lRMA was specific for the circulating mature form of CT

Additive manufacturing of an oxide ceramic by laser beam melting—Comparison between finite element simulation and experimental results

International audienceRecent progress in the application of Laser Beam Melting (LBM) of oxide ceramics has shown promising results. However, a deeper understanding of the process is required to master and control the track development. In this approach numerical modeling could allow higher quality, of additive manufacturing for such materials, to be achieved. The validation of an earlier developed finite element model for LBM of ceramic materials has been established through a comparison with experimental results. The model solves heat and mass transfers whilst accounting for fluid flow due to surface tension and Marangoni convection, as well as tracking the material/gas boundary. The volumetric heat source parameters used in the simulations have been calibrated with an analytical model combined with original in-situ reflectance measurements. Numerical results show good agreement with measurements of melt pool dimensions and shapes. They also provide a coherent description of the evolution of the track morphology when varying the heat source parameters. Track irregularities have also been revealed by simulations at high scanning speed and the balling effect highlighted and explained through similar simulations

First analysis of a numerical benchmark for 2D columnar solidification of binary alloys

International audienceDuring the solidification of metal alloys, chemical heterogeneities at the product scale (macrosegregation) develop. Numerical simulation tools are beginning to appear in the industry, however their predictive capabilities are still limited. We present a numerical benchmark exercise treating the performance of models in the prediction of macrosegregation. In a first stage we defined a "minimal" (i.e. maximally simplified) solidification model, describing the coupling of the solidification of a binary alloy and of the transport phenomena (heat, solute transport and fluid flow) that lead to macrosegregation in a fully columnar ingot with a fixed solid phase. This model is solved by four different numerical codes, employing different numerical methods (FVM and FEM) and various solution schemes. We compare the predictions of the evolution of macrosegregation in a small (10×6 cm) ingot of Sn-10wt%Pb alloys. Further, we present the sensitivities concerning the prediction of instabilities leading to banded channel mesosegregations

Spectral decompositions and \LL^2-operator norms of toy hypocoercive semi-groups

56 pagesInternational audienceFor any $a>0$, consider the hypocoercive generators $y\partial_x+a\partial_y^2-y\partial_y$ and $y\partial_x-ax\partial_y+\partial_y^2-y\partial_y$, respectively for (x,y)\in\RR/(2\pi\ZZ)\times\RR and (x,y)\in\RR\times\RR. The goal of the paper is to obtain exactly the \LL^2(\mu_a)-operator norms of the corresponding Markov semi-group at any time, where $\mu_a$ is the associated invariant measure. The computations are based on the spectral decomposition of the generator and especially on the scalar products of the eigenvectors. The motivation comes from an attempt to find an alternative approach to classical ones developed to obtain hypocoercive bounds for kinetic models

Chemical composition of nanoporous layer formed by electrochemical etching of p-type GaAs

Abstract : We have performed a detailed characterization study of electrochemically etched p-type GaAs in a hydrofluoric acid-based electrolyte. The samples were investigated and characterized through cathodoluminescence (CL), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). It was found that after electrochemical etching, the porous layer showed a major decrease in the CL intensity and a change in chemical composition and in the crystalline phase. Contrary to previous reports on p-GaAs porosification, which stated that the formed layer is composed of porous GaAs, we report evidence that the porous layer is in fact mainly constituted of porous As2O3. Finally, a qualitative model is proposed to explain the porous As2O3 layer formation on p-GaAs substrate

Nouveau mode d'action de l'imatinib mésylate (vers le concept d'immunopharmacologie)

PARIS-BIUP (751062107) / SudocSudocFranceF

Etude de la stabilité d'un médicament radiopharmaceutique (la tétrosfosmine-99mTC (Myoview®-99mTC))

PARIS-BIUP (751062107) / SudocSudocFranceF

Les traitements innovants du mélanome

PARIS-BIUP (751062107) / SudocSudocFranceF

Lupus induits par les médicaments

PARIS-BIUP (751062107) / SudocSudocFranceF