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- Eriksson, Mathilda
(författare)
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Cancer therapy using viral and bacterial proteins as vectors for vaccines or as carriers of cytostatics
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New cancer therapies are urgently needed, since available treatment options today have negative side effects, and cure only about half of the patients with invasive cancer. One, relatively new, option is to vaccinate against cancer, by introducing an antigen that is present on the tumor cells into the patient to stimulate specific immunity against the tumor. For this purpose viral capsid proteins, which can self-assemble into so called virus-like particles (VLPs), can be engineered to contain tumor antigens in the form of DNA, whole protein or peptides and be used as vaccines. Here, VLPs based on murine polyomavirus (MPyV) and murine pneumotropic virus (MPtV) containing the extracellular and transmembrane part of the breast cancer antigen Her2/neu, or the whole prostate cancer antigen PSA, have been produced. As mentioned above there are side effects with cancer treatment, and the use of the common cytostatic anti-cancer drug Cisplatin has a number of side effects, including; nephrotoxicity (kidney damage); neurotoxicity (nerve damage); and ototoxicity (hearing loss). To possibly inhibit some of this toxicity we attempted to make use of the “enhanced permeability and retention” (EPR) effect that causes macromolecules to accumulate more in tumor tissue than in normal tissue, since tumor blood vessels are leaky, and tumors lack effective lymphatic drainage. The use of a macromolecule as a carrier for Cisplatin would therefore hold the potential to reduce some of its negative side effects. For this purpose it was investigated whether the macromolecule right-handed coiled coil “RHCC” protein from bacterium Staphylothermus marinus, that can incorporate heavy metals, would also incorporate cisplatin containing the metal platinum. The overall aim of the first three papers in this thesis was to develop and determine pre-clinical efficacy of MPyV- and MPtV-VLPs carrying Her2/neu or PSA against tumors expressing these tumor antigens. The overall aim of paper IV was to investigate RHCC’s potential to carry cisplatin efficiently to tumors, while retaining the cytotoxic effect of the drug. In paper I we demonstrated that homologous vaccination with human Her2/neu-VLPs was more efficient against outgrowth of human Her2/neu-expressing tumors than heterologous vaccination with rat Her2/neu-VLPs, while against rat Her2/neu-tumors, rat Her2/neu-VLPs were more efficient. Furthermore, we observed that vaccination with MPtVLPs was more efficient than vaccination with MPyVLPs, and that Her2MPtVLPs could be used for therapeutic vaccination. In paper II we demonstrated that both CD4+ and CD8+ T cells are involved in the tumor protective response after Her2MPtVLP vaccination. In paper III immunization with PSA-MPyVLPs, given together with CpG and loaded onto dendritic cells, was shown to protect against outgrowth of PSA-expressing tumor cells. In paper IV RHCC was shown to incorporate cisplatin, and the complex entered human tumor cells, while retaining the cytotoxic potential of the drug both in vitro and in vivo. In conclusion, in this thesis it is shown that VLPs based on MPyV and MPtV were efficient vectors for tumor antigens in cancer vaccination, evoking both CD4+ and CD8+ cell responses. In addition, we show that RHCC can function as a carrier for cisplatin, and that it could potentially reduce some of the negative side effects with cisplatin treatment.
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| 2. |
- Eriksson, Mathilda, 1984-
(författare)
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Mitigating climate change with forest climate tools
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper develops the FRICE, a framework that determines optimal levels of forest climate tools in the context of global climate policy. The paper integrates afforestation and avoided deforestation into the well-known global multi-regional integrated assessment model, RICE-2010. The paper finds that climate forest tools can play an essential role in global climate policy and that this role is increasingly important under stringent temperature targets. Under a 2_C temperature target, the model reveals that emission reductions from avoided deforestation are quickly exhausted whereas afforestation is capable of substantially reducing emission reductions in both the medium and long run. The model also indicates that the most significant reductions in emissions from avoided deforestation and afforestation can be achieved by focusing policy efforts on tropical forests.
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| 3. |
- Eriksson, Mathilda, 1984-, et al.
(författare)
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Pricing forest carbon : implications of asymmetry in climate policy
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we use an integrated assessment model to examine the implications of not recognizing, and partially recognizing forest carbon in climate policy. Specifically, we investigate the impact of an asymmetric carbon policy that recognizes emissions from fossil fuels while ignoring emissions from forests. We additionally investigate the relative importance of not recognizing positive emissions from a reduction in the stock of forest biomass, or of not recognizing negative emissions from the growth of forest biomass. We show that asymmetric carbon policies lead to lower levels of welfare, as well as higher emissions and carbon prices. This occurs because the forest resource will be allocated inefficiently under these carbon policies. Broadly, we find that when the social planner does not account for neither positive or negative forest emissions, the planner will set bioenergy levels that are too high and afforestation and avoided deforestation levels that are too low. Our results further reveal that not recognizing forest emissions leads to larger welfare losses than not recognizing sequestration.
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| 4. |
- Eriksson, Mathilda, 1984-
(författare)
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The Role of the Forest in Climate Policy
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AbstractIn Paper [I], I develop the FOR-DICE model to analyze optimal global forest carbon management. The FOR-DICE is a simple framework for assessing the role of the boreal, tropical, and temperate forests as both a source of renewable energy and a resource to sequester and store carbon. I find that forests play an important role in reducing global emissions, especially under ambitious climate targets. At the global level, efforts should focus on increasing the stock of forest biomass rather than increasing the use of the forest for bioenergy production. The results also highlight the important role of reducing tropical deforestation to reduce climate change.In Paper [II], I develop the FRICE to investigate the role of two key efforts to increase the stock of forest biomass, namely, afforestation and avoided deforestation. FRICE is a multi-regional integrated assessment model that captures the dynamics of forest carbon sequestration in a transparent way and allows me to investigate the allocation of these actions across space and time. I find that global climate policy can benefit considerably from afforestation and avoided deforestation in tropical regions, and in particular in Africa. Avoided deforestation is particularly effective in the short run while afforestation provides the largest emissions reductions in the medium run. This paper also highlights the importance of not solely relying on avoided deforestation as its capacity to reduce emissions is more limited than afforestation, especially under more stringent temperature targets.In Paper [III], we investigate how uncertainties linked to the forest affect the optimal climate policy. We incorporate parameter uncertainty on the intrinsic growth rate and climate effects on the forest by using the state-contingent approach. Our results show that forest uncertainty matters. We find that the importance of including forest in climate policy increases when the forest is subject to uncertainty. This occurs because optimal forest response allows us to reduce the costs associated with uncertainty.In Paper [IV], we explore the implications of asymmetries in climate policy arising from not recognizing forest carbon emissions and sequestration in the decision-making process. We show that not fully including carbon values associated with the forest will have large effects on different forest controls and lead to an increase in emissions, higher carbon prices, and lower welfare. We further find, by investigating the relative importance of forest emissions compared to sequestration, that recognizing forest emissions from bioenergy and deforestation is especially important for climate policy.
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| 5. |
- Eriksson, Mathilda, 1984-, et al.
(författare)
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When not in the best of worlds : uncertainty and forest carbon sequestration
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- It is argued that the forest can provide low-cost options to reduce the atmospheric CO2 concentration. However, many dimensions of the future dynamics of the forest, and its interactions with climate change are still not well understood. This paper provides new insights into how these types of uncertainties affect the optimal climate policy. We model uncertainty over several key forest parameters by using the novel state-contingent approach. Our main results show that the importance of including optimal forest controls in climate policy increases when the dynamics of the forest are uncertain. Ignoring uncertainties concerning the forest will lead to biased estimates of the social costs of carbon and be misleading when evaluating climate policies. Conversely, recognizing forest uncertainties and its potential to mitigate climate change will lead to a robust policy where the cost of uncertainty to a large extent can be avoided.
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| 6. |
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