The SPL (II) at CERN, a Superconducting 3.5 GeV H- Linac

A revision of the physics needs and recent progress in the technology of superconducting (SC) RF cavities have triggered major changes in the design of a SC H-linac at CERN. With up to 5MW beam power, the SPL can be the proton driver for a next generation ISOL-type radioactive beam facility (âEURISOLâ) and/or supply protons to a neutrino () facility (conventional superbeam + beta-beam or -factory). Furthermore the SPL can replace Linac2 and the PS booster (PSB), improving significantly the beam performance in terms of brightness, intensity, and reliability for the benefit of all proton users at CERN, including LHC and its luminosity upgrade. Compared with the first conceptual design, the beam energy is almost doubled (3.5GeV instead of 2.2 GeV) while the length is reduced by 40%. At a repetition rate of 50 Hz, the linac reuses decommissioned 352.2MHz RF equipment from LEP in the low-energy part. Beyond 90MeV the RF frequency is doubled, and from 180MeV onwards high-gradient SC bulkniobium cavities accelerate the beam to its final energy of 3.5GeV. This paper presents the overall design approach, together with the technical progress since the first conceptual design in 2000

Conceptual design of the SPL II: A high-power superconducting H−H^- linac at CERN

An analysis of the revised physics needs and recent progress in the technology of superconducting RF cavities have led to major changes in the speci cation and in the design for a Superconducting Proton Linac (SPL) at CERN. Compared with the rst conceptual design report (CERN 2000012) the beam energy is almost doubled (3.5 GeV instead of 2.2 GeV), while the length of the linac is reduced by 40% and the repetition rate is reduced to 50 Hz. The basic beam power is at a level of 45MW and the approach chosen offers enough margins for upgrades. With this high beam power, the SPL can be the proton driver for an ISOL-type radioactive ion beam facility of the next generation (`EURISOL'), and for a neutrino facility based on superbeam C beta-beam or on muon decay in a storage ring (`neutrino factory'). The SPL can also replace the Linac2 and PS Booster in the low-energy part of the CERN proton accelerator complex, improving signi cantly the beam performance in terms of brightness and intensity for the bene t of all users including the LHC and its luminosity upgrade. Decommissioned LEP klystrons and RF equipment are used to provide RF power at a frequency of 352.2 MHz in the lowenergy part of the accelerator. Beyond 90 MeV, the RF frequency is doubled to take advantage of more compact normal-conducting accelerating structures up to an energy of 180 MeV. From there, state-ofthe- art, high-gradient, bulk-niobium superconducting cavities accelerate the beam up to its nal energy of 3.5 GeV. The overall design approach is presented, together with the progress that has been achieved since the publication of the rst conceptual design report

Antibody Responses to NY-ESO-1 in Primary Breast Cancer Identify a Subtype Target for Immunotherapy

The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)− invasive ductal carcinomas of high grade, including both HER2− and HER2+ tumors. In line with these results, we detected ESO expression in 20% of primary HR− BC, including both ESO Ab+ and Ab− patients, but not in HR+ BC. Interestingly, whereas expression levels in ESO+ BC were not significantly different between ESO Ab+ and Ab− patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR− (HER2− or HER2+) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy

NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment

Spontaneous CD4+ T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4+ T cells in EOC patients with spontaneous immune responses to the antigen are prevalently TH1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer+ cells ex vivo, at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer+ cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25+FOXP3+Treg. Thus, spontaneous CD4+ T-cell responses to ESO in cancer patients are prevalently of TH1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines

Distinct subsets of dendritic cells resembling dermal DCs can be generated in vitro from monocytes, in the presence of different serum supplements.

International audienceWe recently demonstrated that dendritic cells (DCs) can be generated from monocytes in the presence of high concentrations of human serum (HS), provided the extra-cellular pH is maintained at plasma values. Because monocyte-derived DCs (Mo-DCs) can also be generated in the presence of fetal calf serum (FCS) or serum-free medium, we have investigated whether these different culture supplements influence DC generation. With this aim, purified monocytes were cultured with GM-CSF plus IL-4 for 6 days and were further exposed to TNF-alpha for 2 additional days, in the presence of HS, autologous plasma (AP), FCS, or X-VIVO 20, a serum-free medium. Our results show that good yields of functionally mature DCs can reproducibly be obtained in the presence of HS or AP, as assessed by CD83 and CD86 up-regulation, dextran-FITC uptake, allogeneic MLR assays and the induction of an autologous response. Interestingly, the effect of serum on DC generation was probably not only quantitative, but also qualitative, since (i) the majority of HS- or AP-cultured DCs expressed CD83 with very weak levels of CD1a, whereas CD83+ DCs cultured in FCS or X-VIVO were mostly CD1a++; (ii) HS- and AP-cultured DCs were much more granular and heterogeneous than FCS- or X-VIVO-cultured DCs, and (iii) the presence of Birbeck-like granules was preferentially observed in HS- or AP-cultured DCs, as assessed by electron microscopy. That these different cells resemble dermal DCs (DDCs) was further supported by the observations that most of the cells displayed intracytoplasmic FXIIIa in the absence of Lag antigen, and expressed E-cadherin at very low levels. Altogether, our results indicate that starting from the same monocytic population, different subsets of DCs can be generated, depending on the culture conditions. Thus, HS or AP favors the generation of fully mature DCs that resemble activated dermal DCs, whereas FCS, or X-VIVO preferentially leads to the generation of less mature CD1a++ dermal-like DCs