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

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

Physicochemical studies regarding the utilization of wood- and peat-based fly ash

Abstract The main aim of the European Union’s waste legislation and the corresponding Finnish waste legislation is to reduce the production of waste. Further, the aims of the European Union’s growth strategy are to reduce the production of greenhouse gases, increase the use of renewable energy, and improve energy efficiency. According to the renewed Waste Tax Act, a waste tax has to be paid on all fly ashes that are deposited in landfills in Finland. A large amount of wood- and peat-based fly ashes are formed annually in Finland, and the amount is likely to increase in the future due to the increasing use of renewable energy. Previously, these ashes have mainly been deposited in industrial landfills, but the need to utilize the fly ashes has increased recently due to changes in waste legislation. In this thesis, several issues related to the utilization of wood- and peat-based fly ash were studied, with the general objective of improving the utilization potential of such ashes. As the first stage of this research, the suitability of willow ash for use as a fertilizer was studied. Willow ash would be well suited for use as a fertilizer due to its very high nutrient content. However, cadmium, a heavy metal, was found to be enriched in the ashes of the studied willow species. Due to this, special attention should be paid when choosing willow species for energy production. In the second stage of the research, the possibility of improving the strength development of wood- and peat-based fly ashes, as well as the possibility of stabilizing fly ash containing high amounts of heavy metals via the addition of cement and/or alkali activation, was investigated. Strength development was found to be dependent on the amount of reactive calcium and the ratio between that amount of reactive calcium and the sum of the reactive silicon, aluminum, and sulfur (Ca/(Si + Al + S)). The studied methods performed well in terms of stabilizing barium, copper, lead, and zinc. During the next stage, the effect of different chemical digestion methods, which are regulated by the Finnish waste legislation, on the utilization potential of fly ash was studied. The digestion method had a significant impact on the results of the potassium content analysis, which could affect the possibility of using fly ash as a fertilizer. As the final stage of the research, the co-granulation of ash with sewage sludge and lime was studied. From a technical point of view, the co-granulation was successful, although the compressive strength of the granules was low. Additionally, an insufficient nitrogen content was achieved with a sludge addition of 20-40 weight%.Tiivistelmä Euroopan unionin jätelainsäädännön ja sitä vastaavan suomalaisen lainsäädännön tavoitteena on ehkäistä jätteiden muodostumista. Euroopan Unionin kasvustrategian tavoitteena on vähentää kasvihuonekaasupäästöjä, lisätä uusiutuvan energian käyttöä ja parantaa energiatehokkuutta. Uudistetun jäteverolain mukaan kaikista kaato-paikoille sijoitetuista lentotuhkista tulee Suomessa maksaa jäteveroa. Suomessa puu- ja turveperäisiä lentotuhkia muodostuu vuosittain suuria määriä ja määrä tulee vielä kasvamaan uusiutuvan energiankäytön lisääntyessä. Aiemmin nämä tuhkat ovat päätyneet pääasiassa läjitykseen teollisuuden kaatopaikoille, mutta muuttuneen jätelainsäädännön seurauksena tarve hyödyntää lentotuhkia on lisääntynyt. Tässä väitöstyössä tutkittiin puu- ja turveperäisten tuhkien hyödyntämiseen liittyviä kysymyksiä. Työn yleistavoitteena oli parantaa tuhkien hyödyntämis-mahdollisuuksia. Tutkimuksen ensimmäisessä vaiheessa tutkittiin pajutuhkan soveltuvuutta lannoitteeksi. Pajutuhka soveltuisi hyvin lannoitteeksi erittäin hyvien ravinne-pitoisuuksien ansiosta. Raskasmetalleista kadmiumin havaittiin kuitenkin rikastuvan tutkittujen pajulajien tuhkiin. Tähän tulisi kiinnittää erityishuomiota, kun pajulajeja valitaan energiantuotantoa varten. Tutkimuksen toisessa vaiheessa selvitettiin mahdollisuutta parantaa turpeen ja puun lentotuhkien lujittumista sekä raskasmetallipitoisen lentotuhkan stabiloimista sementtilisäyksen ja/tai alkaliaktivoinnin avulla. Lujuuden kehitys riippui reaktiivisen kalsiumin määrästä sekä reaktiivisen kalsiumin määrän ja reaktiivisten piin, alumiinin ja rikin määrien summan välisestä suhteesta (Ca/(Si + Al + S)). Tutkitut menetelmät toimivat hyvin bariumin, kuparin, lyijyn ja sinkin stabiloinnissa. Seuraavassa vaiheessa selvitettiin Suomen lainsäädännössä määritettyjen kemiallisten hajotusmenetelmien vaikutusta tuhkan hyödyntämispotentiaaliin. Hajotusmenetelmällä oli suuri merkitys kaliumin pitoisuutta määritettäessä, mikä voi vaikuttaa lentotuhkan hyödynnettävyyteen lannoitteena. Viimeisessä vaiheessa tutkittiin tuhkan yhteisrakeistusta lietteen ja kalkin kanssa. Teknisesti yhteisrakeistus onnistui hyvin, mutta rakeiden puristuslujuus oli alhainen. Lisäksi 20 - 40 paino% lietelisäyksellä ei rakeisiin saatu riittävän korkeaa typpipitoisuutta

New nitrogen-containing recycled fertilizers:bioavailability of nutrients and harmful elements

Abstract Environmental policies of the European Union aim to increase recycling and re-use of waste-streams. One of the economically most profitable ways of re-using waste is to use it as a fertilizer. In this study, recycled nitrogen fertilizers were manufactured from industrial side-streams (sawdust, fly-ash, ammonium sulfate and lignosulfonate). A sequential extraction procedure was applied to all the products tested in this paper to make sure that the environmental requirements of a recycled fertilizer would be fulfilled. A mass fraction of up to 7.0% of nitrogen was achieved with sawdust granule and 7.2% with fly-ash-sawdust granule, indicating that the granules would be well suited to be used as nitrogen-containing fertilizers. Nitrogen release from sawdust granule was more controlled than from commercial salpetre. Sawdust combined with fly-ash can hence give a balanced nutrient mix when used together. Bioavailabilities and pseudo-total contents of harmful elements (As, Cd, Cr, Cu, Ni, Pb, and Zn) were small in all granules and cause no harm in field or forest fertilizer use

Utilization of fly ashes from fluidized bed combustion::a review

Abstract Traditionally fly ash is thought to be glassy, spherical particle originating from pulverized coal combustion (PCC) at temperature up to 1700 °C. However, nowadays fluidized bed combustion (FBC) technology is spreading quickly around the world as it is an efficient and environmentally friendly method. FBC is also able to utilize mixtures of low-grade solid fuels (e.g., coal, lignite, biomass, and waste) that have fluctuating quality, composition, and moisture contents. However, this leads to a high variation in the produced fly ash quality, unlike PCC fly ash, and hence challenges when attempting to utilize this fly ash. In this study, the utilization of fluidized bed combustion fly ash (FBCFA) was reviewed using the Scopus database. The most promising utilization target for FBCFA from biomass combustion is as a fertilizer and soil amendment. In construction, the FBCFA from various fuels is utilized as cement replacement material, in non-cement binders, as lightweight aggregates and cast-concrete products. Other types of construction applications include mine backfilling material, soil stabilizer, and road construction material. There are also other promising applications for FBCFA utilization, such as catalysts support material and utilization in waste stabilization

Alkali-activated materials as catalysts for water purification

Abstract In this study, novel and cost-effective alkali-activated materials (AAMs) for catalytic applications were developed by using an industrial side stream, i.e., blast furnace slag (BFS). AAMs can be prepared from aluminosilicate precursors under mild conditions (room temperature using non-hazardous chemicals). AAMs were synthesized by mixing BFS and a 50 wt % sodium hydroxide (NaOH) solution at different BFS/NaOH ratios. The pastes were poured into molds, followed by consolidation at 20 or 60 °C. As the active metal, Fe was impregnated into the prepared AAMs by ion exchange. The prepared materials were examined as catalysts for the catalytic wet peroxide oxidation (CWPO) of a bisphenol A (BPA) aqueous solution. As-prepared AAMs exhibited a moderate surface area and mesoporous structure, and they exhibited moderate activity for the CWPO of BPA, while the iron ion-exchanged, BFS-based catalyst (Fe/BFS30-60) exhibited the maximum removal of BPA (50%) during 3 h of oxidation at pH 3.5 at 70 °C. Therefore, these new, inexpensive, AAM-based catalysts could be interesting alternatives for catalytic wastewater treatment applications

Bioavailability of nutrients and harmful elements in ash fertilizers:effect of granulation

Abstract Environmental policies of the European Union (EU) aim to increase the amount of renewable energy and to improve the use of waste streams. This will increase the amount of fly ash (FA) from biomass combustion, thereby increasing the need for its utilization. Biomass FA is a good fertilizer since it contains most of the nutrients that plants need. Sequential leaching would provide a more accurate assessment of the potential bioavailability of the harmful elements and nutrients than the pseudo-total and/or water-soluble concentration analysis that EU environmental legislation typically requires. This study investigated the effect of granulation and ammonium sulfate addition on the solubility and bioavailability of nutrients and harmful elements from peat and wood co-combustion FA by using sequential leaching and pseudo-total acid digestion. The recoveries of the easily bioavailable nutrients Ca, K, Mg, P, and S as well as the total bioavailability of Ca, K, Mg, and S reduced significantly after granulation. Therefore, granulation reduced the fertilizing effect of FA. The pseudo-total recovery of Ca, Mg, and S reduced after granulation, indicating that these types of FA form some very stable silicate compounds besides the common self-hardening products. Ammonium sulfate addition increased the recoveries of the easily bioavailable nutrients and total bioavailability recoveries of the Ca, K, and Mg back to the same levels as those in FA. The total bioavailability of the harmful elements As, Cd, Cr, Cu, Ni, Pb, and Zn was very low, and this does not limit the usability of FA as a fertilizer

Comparison of standard methods for evaluating the metal concentrations in bio ash

Abstract The current growth strategy and environmental legislation of the European Union both aim to increase the amount of renewable energy and to improve the use of waste streams. These policies mean there will be an increasing need to utilise bio ash. Currently, Finland and Denmark are the only European countries with specific national legislation concerning bio ash use. Sweden has recommendations concerning the use of bio ash fertilisers. Besides having different limit values for harmful elements and nutrients in ash fertilisers, all these countries have different digestion methods that are allowed for element content determinations. This study compared the results of the five digestion methods (aqua regia, nitric acid, nitric/hydrochloric acids, nitric/hydrochloric/hydrogen fluoride acids, and lithium tetraborate fusion) established by Nordic authorities. Two Finnish peat-wood fly ash samples were studied. Our results indicate that the choice of digestion methods produces a significant difference in the obtained heavy metal or nutrient concentration of bio ash, especially regarding the potassium concentration

Precipitation of struvite using MgSO₄ solution prepared from sidestream dolomite or fly ash

Abstract Struvite (NH₄MgPO₄∗6H₂O) is a slow-release fertilizer produced from phosphorus and nitrogen-containing wastewater in the presence of Mg salts. Commercial Mg salts are the single most significant cost of struvite precipitation. In this study, H₂SO₄ formed as an industrial sidestream was used to prepare MgSO₄ solution from waste dolomite (DOL) and fly ash (FA). MgSO₄ solution was then used to precipitate struvite from a synthetic (NH₄)₂HPO₄ solution and from actual industrial process waters. The best results were obtained with real process waters where over 99% of phosphate and about 80% ammonium removals were achieved with both MgSO4 solutions after 30 min of reaction time. A higher molar ratio between Mg and P improved the phosphate removal efficiency, especially with DOL-based MgSO4 solutions; however, it had no practical effect on ammonium removal. The struvite content of precipitates was 75.49% with an FA-based chemical and 60.93% with a DOL-based chemical; other valuable nutrients (Ca, K, S, Fe, Mn, and Cl) were captured in the precipitates. The results indicate that both sidestream-based reagents perform well in struvite precipitation and that the formed precipitates could be used as fertilizers