Call for Applications Autumn, Second

Main supervisor: Adj. Professor Carlos Rogerio Figueiredo, Institute of Biomedicine, University of Turku, InFLAMES Research Flagship, rogerio.defigueiredo@utu.fi

Other supervisor(s):  Kalle Mattila, Department of Clinical Medicine, University of Turku, kalle.mattila@tyks.fi

Pilot project description 

In the adjuvant treatment of metastatic cutaneous melanoma, where therapy is aimed at preventing recurrence after tumor removal, clinical trials comparing targeted therapy (TT) and immune checkpoint inhibitors (ICI) highlight a balance between short-term control and long-term survival. TT rapidly shrinks tumors by blocking melanoma growth pathways, lowering the risk of recurrence for some patients. Meanwhile, ICIs reinvigorate the immune system to attack cancer cells, providing slower but more durable
responses.

When it comes to combining these therapies to achieve better benefits, the order in which they are administered plays a significant role in their effectiveness. One recent clinical trial shows that when TT is used first, it may provide immediate control by shrinking micrometastases in some patients, but it also diminishes the effectiveness of ICI when introduced afterward. Conversely, starting with ICI helps maintain a stronger and more durable immune response, but without the initial rapid tumor control that is typically seen when TT is administered first. In our latest review, we highlight that one of the primary causes of resistance to ICI in melanoma stems from the nature of desert tumors, which are characterized by a lack of antitumor T cells.

Therefore, we hypothesize that TT may contribute to ICI resistance by targeting immune cells responsible to trigger melanoma immunogenicity, suppressing immune response before ICI is introduced.

Our project aims to explore the underlying causes of TT induced ICI resistance in the adjuvant setting, particularly on how it impacts the maintanence of antitumor T cell responses. This knowledge will guide future strategies for rational combinations that retain the initial benefits of TT while supporting the longterm efficacy of ICI. By focusing on the mechanisms through which TT disrupts immune responses, we can
develop optimized approaches that prevent recurrence and improve survival outcomes.

Keywords:

Immune checkpoint therapy, cancer, targeted therapy, cold tumors, anti-PD1, adjuvant therapy, resistance

Main supervisor: M.D., Ph.D. Ilkka Julkunen, University of Turku, InFLAMES Research Flagship, ilkka.julkunen@utu.fi

Other supervisor(s):  Pekka Kolehmainen, Institute of Biomedicine, University of Turku, pekka.j.kolehmainen@utu.fi

Pilot project description:

Avian influenza A viruses (AIV) form a significant pandemic threat for animal and human health. In 2023 Finland suffered from a devastating wild bird and fur animal epidemic that led to the death of thousands of seagulls and water birds as well as culling of more than 500 000 fur animals. Personnel at fur farms, veterinarians and laboratory workers were exposed to circulating avian influenza strains, but no human cases were identified in Finland. EU has purchased 2 million doses of H5N1 type AIV vaccine of which 20 000 doses were intended for human use in Finland. Finland has started public vaccinations with AIV vaccine, with target groups being fur farm workers, poultry industry workers, veterinarians and laboratory workers who are exposed to avian influenza virus in their work. Finnish Institute for Health and Welfare (THL) together with the research group of Ilkka Julkunen at the University of Turku has initiated a clinical follow-up trial on analyzing adaptive immunity induced by AIV vaccine.

The project includes an experimental part in mice with DelSiTech Ltd. (Turku) to study the immunogenicity of the commercial AIV vaccine compared to our own Finnish type AIV H5 protein antigens. The major emphasis is on DelSiTech silica matrix-based slow release of viral antigens that based on preliminary data enhances immune responses after vaccination. The clinical part started in August 2024 and it includes the collection of blood samples before and after a two-dose AIV vaccine regimen. Humoral and cell-mediated immunity will be analyzed with the most modern laboratory methods. The project includes work in the BSL-3 facility of the University of Turku, study visits to DelSiTech and THL (Helsinki), and the project provides the Ph.D. student excellent experience in immunological methods and BSL-3 work. This project is globally the first one to analyze adaptive immunity induced by current avian influenza vaccine and thus the public health impact of the project is highly significant.

Key words: Avian influenza, vaccine, humoral immunity, cell-mediated immunity, clinical trial

Main supervisor: Vilhelmiina Parikka, Turku University Hospital, Department of Pediatrics and Adolescent Medicine; University of Turku, MediCity Research Laboratories, InFLAMES Research Flagship Center and Preclinical Imaging Laboratory at Turku PET Centre, vilpar@utu.fi

Other supervisor(s): Otto Kauko, Turku Bioscience Centre, University of Turku, otkauko@utu.fi

Pilot project description:

Neonatal hypoxic-ischemic encephalopathy is the most severe birth complication and one of the leading causes of death or severe morbidity in newborns, caused by inadequate blood flow and oxygen delivery to the brain during or shortly after birth.

This project aims to provide novel insights into the role of inflammation and to identify novel biomarkers to predict brain injury in the early phase. The project will be carried out at the Neonatal Intensive Care Unit of Turku University Hospital and the MediCity Research Laboratories of the University of Turku.

The project will use samples from our prospective case-control follow-up study at Turku University Hospital. A comprehensive analysis of proteins from patients’ blood samples will be performed to determine how the inflammatory process proceeds during the first hours and days after injury. We plan to perform: 1) targeted analysis of inflammatory and endothelial injury-associated cytokines and other proteins together with markers of neuronal injury using Olink’s proximity extension assay and a novel single molecular array technique (Simoa®) and 2) proteomics and metabolomics analyses of the clinical samples using mass spectrometry at the Turku Proteomics Facility and Turku Metabolomics Centre to facilitate the identification of proteins and changes in the serum metabolome associated with hypoxic-ischemic encephalopathy.

The results of the multiomics analyses will be evaluated as part of the patient’s clinical situation and compared with the level of neurological injury. This project aims to provide the basis for biomarker development, in particular point-of-care testing, to facilitate early identification of the most severely affected individuals who may benefit from therapeutic interventions.

Key word(s):Neonatal, hypoxia, biomarker, neuroinflammation, brain injury, clinical study

Main supervisor:  Assoc Prof Pekka Ruusuvuori, Institute of Biomedicine, University of Turku, pekka.ruusuvuori@utu.fi
Website: https://ruusuvuorilab.utu.fi/

Other supervisor(s): Prof Pekka Taimen, Institute of Biomedicine, University of Turku & Turku University Hospital, InFLAMES Research Flagship, pepeta@utu.fi
Dr. Leena Latonen, Institute of Biomedicine, University of Eastern Finland, leena.latonen@uef.fi
Tapio Lönnberg, Turku BioScience Center & InFLAMES Research Flagship, tapio.lonnberg@utu.fi

Pilot project description:

Immunological landscape of human tissue is typically determined through applying specific histochemical stainings to 2D tissue sections revealing quantity and location of immunologically active cell types. Such measurements can reveal similarities and differences between tissue microenvironments in normal and tumor tissue. Quantification of the tissue microenvironment computationally from immunostained tissue and other spatial measurements is possible using modern tools based on artificial intelligence (AI). Spatial environment within tissue is not, however, two-dimensional – but taking into account the true 3D spatial environment of the tissue sets a significantly more challenging task for the computational tools, which are currently lacking. Here, we set out to develop computational methods for 3D modeling of the immune component in normal and cancerous tissue and to study the immune landscape of tissue quantitatively and through visual exploration using virtual reality (VR).

Specifically, we will model the 3D tissue environment by applying already existing, in-house developed reconstruction pipeline using murine spleen and prostate as the model, develop artificial intelligence based computational methods for quantitative characterization of immunological cells, and visualize the immune component by applying a dedicated VR application already developed in the hosting research group. The work requires interest towards immunology and histology, and skills in machine learning and image analysis using relevant programming environments. The research will be done at the Institute of Biomedicine/UTU secondments to collaborating companies are encouraged. We expect the project to be highly useful for the immunology and cancer research communities, and it has the potential to also advance disease diagnostics. This project has a high level of synergy with several immunology-driven research topics within and beyond the ImmuDocs pilot program. After graduation, the candidate will have highly relevant data science skills for industrial positions.

Keywords: Immunology, immunohistochemistry, 3D histology, artificial intelligence, virtual reality

Main supervisor: Professor Cecilia Soderberg-Naucler, Institute of Biomedicine, University of Turku, InFLAMES Research Flagship, cecilia.naucler@utu.fi

Other supervisor(s): Assistant Professor Xiang-Guo Li, Turku PET Centre, li.xiang-guo@tyks.fi
Associate Professor Dhifaf Sarhan, Karolinska Institutet, dhifaf.sarhan@ki.se
Professor Jiri Bartek, Karolinska Institutet, jb@CANCER.DK

Pilot project description

A number of different tumors have today been shown to be positive for cytomegalovirus (CMV) proteins; for example, more than 90% of brain tumors, neuroblastoma, sarcomas, breast, colon, prostate and ovarian cancer are CMV positive. Both primary tumors as well as >95% of lymphode and distant metastases from breast and colon cancer are virus positive, while non-tumor cells in healthy tissues surrounding the primary tumors or their metastases are virus negative. Thus, CMV positivity is confined to tumor cells and may therefore provide a novel therapy target in cancer treatment.

As a proof of concept model, we and others have shown that anti-viral therapy or vaccination against CMV in patients with glioblastoma highly improve expected survival time. We found that anti-viral therapy prevents radiation induced CMV reactivation that occurs in almost 50% of these patients, of which a majority
develop rapid tumor recurrence within 3 months. This is fully preventable with anti-viral therapy and show promise to enhance survival time from 13.5 to 29.7 months.

We hypothesize that a combined therapy with anti-viral drugs and an immune based targeted approach towards CMV infected cells in the tumor, will further increase the efficacy of anti-CMV therapy in CMV positive cancer patients and improve treatment outcome. This project intends to compare the efficacy of three immune based therapies; a peptide T cell vaccine, a CMV targeted antibody therapy (conjugated with a toxin) and an adoptive NKG2C therapy, with or without combination with anti-CMV therapy in glioblastoma and breast cancer mouse models. The PhD candidate will study both human xenograft tumors and MCMV indcuced metastatic disease to determine the most effective immune-based anti-CMV approach for advancement to a clincial phase I trial. The research is conducted at Medicity, University of Turku.

Key words: Glioblastoma, breast cancer, cytomegalovirus, peptide vaccine, NK cells, T cells