Harmonisation of short-term in vitro culture for the expansion of antigen-specific CD8+ T cells with detection by ELISPOT and HLA-multimer staining

Ex vivo ELISPOT and multimer staining are well-established tests for the assessment of antigen-specific T cells. Many laboratories are now using a period of in vitro stimulation (IVS) to enhance detection. Here, we report the findings of a multi-centre panel organised by the Association for Cancer Immunotherapy Immunoguiding Program to investigate the impact of IVS protocols on the detection of antigen-specific T cells of varying ex vivo frequency. Five centres performed ELISPOT and multimer staining on centrally prepared PBMCs from 3 donors, both ex vivo and following IVS. A harmonised IVS protocol was designed based on the best-performing protocol(s), which was then evaluated in a second phase on 2 donors by 6 centres. All centres were able to reliably detect antigen-specific T cells of high/intermediate frequency both ex vivo (Phase I) and post-IVS (Phase I and II). The highest frequencies of antigen-specific T cells ex vivo were mirrored in the frequencies following IVS and in the detection rates. However, antigen-specific T cells of a low/undetectable frequency ex vivo were not reproducibly detected post-IVS. Harmonisation of the IVS protocol reduced the inter-laboratory variation observed for ELISPOT and multimer analyses by approximately 20 %. We further demonstrate that results from ELISPOT and multimer staining correlated after (P < 0.0001 and R(2) = 0.5113), but not before IVS. In summary, IVS was shown to be a reproducible method that benefitted from method harmonisation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-014-1593-0) contains supplementary material, which is available to authorized users

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

The SPIRAL radioactive ion beam facility

This document describes the scientific goals as well as the technical choices of the SPIRAL project (Système de Production d'Ions Radioactifs et d'Accélération en Ligne)

Manipulation de nanofils de silicium à partir de nano robots

Nous présentons dans cet article une proposition de travaux pratiques sur la manipulation de nanofils de silicium individuels à partir de nano-robots pilotés par ordinateur. Ces nano-robots sont installés dans l’enceinte d’un microscope électronique à balayage. Le contrôle des nano-robots se fait par ordinateur via un module électronique d’interface

Tuning the Photoelectrocatalytic Hydrogen Evolution of Pt-Decorated Silicon Photocathodes by the Temperature and Time of Electroless Pt Deposition

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Intrinsic magnetic properties of BixCo2−xMnO4 spinels obtained by short-time etching

International audienceThe structural and magnetic properties of the cubic spinel oxide Co2MnO4 (Fd3m space group) doped with different concentrations of bismuth, were investigated by X-ray diffraction and SQUID magnetometry. The Bi3+ ions entering into the CoIII octahedral sites do not alter the effective moment, μeff ∼8.2 μB, whereas both the magnetization M50 kOe at the highest field (50 kOe) and the field-cooled MFC magnetizations increased when increasing the Bi content. The ferrimagnetic character of the parent compound, Co2MnO4, is maintained for all materials although the antiferromagnetic interactions Co2+–Co2+ are affected, resulting in higher values of the Curie–Weiss temperature. Due to the large ionic radius of Bi, octahedra distortions occur as well as valence fluctuations of the Mn ions, giving rise to Jahn-Teller effects and enhancing the exchange interactions. The off-center Bi3+ ion is responsible of non-centrosymmetric charge ordering and should lead to multiferroïsme conditions for the BixCo2−xMnO4 material

Complex Epitaxy of Tetragonal Tungsten Bronze K-Ta-Nb-O Nanorods

International audienceTetragonal tungsten bronze (TTB) phases possess numerous important properties (ferroelectricity, multiferroicity, piezoelectricity, optical nonlinearity, electro-optics) that can be achieved by modifying their composition, in addition to their ability to grow as very anisotropic crystals. In this study, K-5.06(Ta0.57Nb0.43)(10.99)O-30 tetragonal tungsten bronze phase thin films were grown by a pulsed laser deposition technique on (001)SrTiO3 and R-plane sapphire substrates. The films grew according to two modes with respect to the substrate surface, that is, as vertical nanorods with the [001] direction perpendicular to the substrate surface and as horizontal nanorods with the [001] orientation parallel to the substrate surface and out-of-plane direction. Both vertical and horizontal nanorods present epitaxial relationships with the substrates. Careful study of epitaxial relationships showed a complex growth on both substrates that can be described in the framework of domain matching epitaxy resulting in several antiphase domain formations for both kinds of nanorods. These particular configurations are due to a high degree of coincidence between cations (anions) of the film with those of the substrate. This study shows the ability of ferroelectric TTB phases to grow as one-dimensional objects with the possibility to tailor their polarization direction either normal to or parallel to the substrate surface

Experimental investigation of the U-Zr-Al ternary phase diagram: Isothermal sections at 673 K and 1073 K.

International audienceIsothermal sections at 673 K and 1073 K of the ternary U-Zr-Al system were established in the whole concn. range, by means of powder X-ray diffraction, SEM-energy dispersive X-ray spectroscopy and DTA. All measured compns. and unit-cell refinements were performed at room temp. from quenched samples annealed at 1073 K and 673 K for four and eight weeks resp. For both temps., the Al-rich corner of the phase diagram is characterized by extended homogeneity ranges due to mutual exchange between U and Zr in UAl3 (cubic, AuCu3-type) and in the Laves phase UAl2 (cubic, MgCu2-type). Minute U soly. in ZrAl2 (hexagonal, MgZn2-type) and in Zr2Al (hexagonal, Ni2In-type) was evaluated to be of the order of 1 at.% U. For the other binary compds., the soly. of the third component was found negligible. At 1073 K, the solid soln. based on γU (cubic, W-type) which covers the U-Zr binary axis up to 95.5 at.% Zr, allows also some limited soly. of Al [max. of 5 at.%]. For Al-content below 66 at.%, most of the phase relations comprise equil. between the Zr-Al binaries and the γ(U,Zr,Al) solid soln. At 673 K, the U-Zr axis is found in agreement with the literature data and no Al soly. could be detected in αU, αZr and UZr2 (δ phase). The phase relations are mainly established between Zr-Al binaries and αU. For monolithic UMo fuel with a Zr diffusion barrier foil cladded with Al, the main interaction product is expected to involve the U-based alloy with the Zr-Al binary compds. and the pseudo-binary U1-xZrxAl2 and U1-xZrxAl3 phases