36 research outputs found

    Validation of biomarkers to predict response to immunotherapy in cancer: Volume I — pre-analytical and analytical validation

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    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    MOCVD growth of GaAs-Ga1-xAlxAs structures for microwave MESFET's

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    MOCVD GaAs-Ga1-xAlxAs epitaxial structures to fabricate MESFET's have been successfully grown in a low pressure MOCVD system. The growth parameters were optimized to obtain very high uniform epitaxial layers (o - 2%). MESFET's were fabricated and the devices with heterobuffer layer showed good transconductance and linearity as compared to conventional GaAs buffered structures. A 7.7 dB gain was performed at Idss/2 at 18 GHz. However the breakdown voltage has to be improved by lowering the back­ground doping in the Ga1-xAlxAs buffer layer

    Advanced Triple Junction Solar Cells with Innovative Assembly for space application: Development and flight test

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    Triple junction solar cells based on InGaP/GaAs/Ge are the baseline for the space application. This paper reports the achievement in terms of development, characterization and in-flight experience for two new concepts of multijunction solar cells developed at CESI and experimented on board of a cubesat developed at Sapienza University: the triple junction solar cells with integral assembly (CTJ-AI) and the triple junction solar cells with enhanced resistance against radiation (CTJ-EOL)

    External Quantum Efficiency and First Results of Electric Performance Measurements on a Quadruple Junction Space Solar Cell

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    External Quantum Efficiency (EQE) and Current-Voltage (I-V) measurements of a monolithic quadruple junction (4J) space solar cell AlGaInP (J1)/ AlInGaAs (J2) / InGaAs (J3) / Ge (J4) manufactured by CESI (Milano, Italy) have been performed at INTA-Spasolab. In order to determine electrical cell performance of this 4J solar cell type under AM0 irradiance and cell temperature standard conditions, the external quantum efficiency (EQE) measurement system and steady-state solar simulators at the cell testing laboratory INTA-Spasolab are to be upgraded. The purpose of this work is to present both the upgrading of INTA-Spasolab facilities and the results of the characterization of a 4J solar cell under development

    External Quantum Efficiency and First Results of Electric Performance Measurements on a Quadruple Junction Space Solar Cell

    No full text
    External Quantum Efficiency (EQE) and Current-Voltage (I-V) measurements of a monolithic quadruple junction (4J) space solar cell AlGaInP (J1)/ AlInGaAs (J2) / InGaAs (J3) / Ge (J4) manufactured by CESI (Milano, Italy) have been performed at INTA-Spasolab. In order to determine electrical cell performance of this 4J solar cell type under AM0 irradiance and cell temperature standard conditions, the external quantum efficiency (EQE) measurement system and steady-state solar simulators at the cell testing laboratory INTA-Spasolab are to be upgraded. The purpose of this work is to present both the upgrading of INTA-Spasolab facilities and the results of the characterization of a 4J solar cell under development
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