Institute News

Researchers investigate the control center for maintaining immune cell fitness 

(Vienna, 14.03.2024) The endoplasmic reticulum in human immune cells is the topic of a current research project at the St. Anna Children’s Cancer Research Institute (CCRI). This highly complex network of membrane structures is where the cells proteins are produced and the quality control processes that ensure these proteins function properly; important reactions for maintaining cell fitness are also coordinated here. A team led by immunologists Kaan Boztug, MD, Scientific Director of the St. Anna Children’s Cancer Research Institute, and Senior Postdoc Michael Kraakman are now investigating how this important component of the cell is linked to a newly discovered immunodeficiency disorder and the tendency to develop tumors (tumor predisposition).

Genetic predispositions lead to tumors much more frequently in children than in adults. At least ten per cent of all childhood cancers develop in this way. Congenital immunodeficiencies, for example, can favor the development of tumors because cancer cells have a much easier time with a poorly functioning immune defense than under normal circumstances. This is why immunology has become a central component of modern pediatric cancer research. 

With the support of the Austrian Science Fund FWF, research is now being conducted on a new genetic defect that negatively impacts the function of the endoplasmic reticulum and renders cells, particularly those of the adaptive immune system as debilitated. The scientists have identified four patients with this defect in their immune system: These four children have a mutation in a gene that encodes a protein involved in protein folding and protein degradation. 

Both processes are essential for the health of the cell: protein folding is the process by which proteins obtain their three-dimensional structure and is the prerequisite for the flawless function of the protein. Protein degradation is crucial to remove aged, malformed and/or obsolete proteins to make room for new, correctly folded proteins. Clinically, the immunodeficiency results in frequent infections in all four cases and a predisposition to lymphoma.

New Zealand expert at the St. Anna Children’s Cancer Research Institute

The cell biologist Michael Kraakman, originally from New Zealand and the head of the FWF project, studied at the University of Otago and completed his PhD at the Monash University in Melbourne, Australia, before a postdoctoral project took him to Columbia University in New York. Since 2019, he has been working at the St. Anna Children’s Cancer Research Institute in the group of the Scientific Director Kaan Boztug. The study in question was started back then with initial data from two siblings, one of whom was able to survive the disease thanks to a bone marrow transplant. 

Their work has shown that the gene mutation influences key processes in the endoplasmic reticulum, slows down the work of lymphocytes and reduces their survival. The endoplasmic reticulum provides proteins needed by the immune cells to respond and adapt quickly to invaders. However, for a proper immune response, these proteins must be correctly folded. Kraakman says: “If the protein produced fails to attain the correct three-dimensional shape, the cell must label it as misfolded and remove it.” If the cell were not to do so, misfolded proteins would accumulate within the cell, hindering the ongoing production of new proteins and impeding the cell to function appropriately. Therefore, the removal of misfolded proteins is vital.

Boztug emphasizes the “lymphoma predisposition of these children with this mutation”. “This is why these newly discovered diseases are so relevant in contemporary pediatric cancer research,” he says.

United Fight Against Osteosarcoma: Innovative T-Cell Therapy Research

(Vienna, March 12, 2024) The St. Anna Children’s Cancer Research Institute is at the forefront of a groundbreaking research initiative targeting osteosarcoma, the most prevalent aggressive bone cancer in children and young adults. The project, DART2OS, spearheaded by the Institute of Molecular Pathology (IMP) and supported by the Austrian Science Fund’s “Emerging Fields” excellence initiative, aims to revolutionize osteosarcoma treatment with advanced T-cell therapies over the next five years.

Osteosarcoma’s complexity, characterized by its aggressive nature and multiple genetic mutations, has challenged scientists and hindered targeted therapeutic advancements. The conventional chemotherapy approach has seen minimal progress over four decades. DART2OS is set to change this landscape by developing cutting-edge cellular therapies that empower the immune system to combat this challenging cancer effectively.

Funded with 5.7 million euros, the project is part of the FWF’s “Emerging Fields” program, highlighting its significance and the competitive nature of the funding. Johannes Zuber, PhD of the IMP leads a consortium of experts, including Sabine Taschner-Mandl, PhD from St. Anna Children’s Cancer Research, Anna Obenauf, PhD from IMP, Johannes Huppa, PhD from the Medical University of Vienna, Dietmar Rieder, PhD from the Medical University of Innsbruck, and Michael Traxlmayr, PhD  from the University of Natural Resources and Life Sciences. Their collective expertise is poised to make significant strides in cancer research, particularly in developing TCR-T-cell therapies.

Directing T-Cells Against the Tumor 

The project’s innovative approach involves a detailed analysis of tumor-specific mutations and their visibility to T-cells, which are often inhibited by the tumor itself. By examining 20 to 30 detailed samples, the research team aims to uncover why osteosarcomas evade immune system attacks, setting a precedent for rare cancer research.

DART²OS  ‘s mission extends beyond osteosarcoma. By harnessing patient-specific TCR-T-cells capable of recognizing and destroying cancer cells, the project lays the groundwork for personalized immunotherapies that could transform treatment protocols for various cancers. Dr. Johannes Zuber emphasizes the collaborative effort to translate personalized TCR-T-cell therapies into viable treatments for pediatric cancers, marking a significant leap forward in oncology.

International Women’s Day: Spotlight on the Power of Women 

(Vienna, 8.3.2024) In celebration of International Women’s Day, we proudly highlight the incredible women of St. Anna Children’s Cancer Research Institute, where an inspiring 67% of our dedicated team members are women. Among them stand Principal Investigators Eleni Tomazou and Sabine Taschner-Mandl, whose contributions shape the landscape of pediatric cancer research.

Eleni Tomazou, recipient of the esteemed ERC grant, champions a unique “build it, to understand it” methodology. Acknowledging the challenge of comprehending tumors, she pioneers modeling childhood cancer, aiming to unravel complexities and create accessible platforms for drug testing.

Equally impactful, Sabine Taschner-Mandl has made significant contributions published in renowned journals. As a Principal Investigator leading the MONALISA project, Taschner-Mandl spearheads collaboration among 24 top European research institutions in pediatric oncology. This Horizon Europe-funded initiative focuses on studying the benefits of innovative diagnostic methods, introducing liquid biopsies for children with neuroblastoma in a clinical setting for the first time.

We are grateful to have Eleni and Sabine on our team, and equally thankful for all the other women at St. Anna CCRI who bring a diversity of perspectives and skills. Their dedication and professionalism are irreplaceable, significantly contributing to shaping the future of pediatric cancer treatment.

On this day, we also stand in solidarity not only with the strong women on our team but also with those women worldwide still fighting for the respect and recognition they deserve. May International Women’s Day serve as a poignant reminder that inclusion propels us all forward.

Why Rare Disease Research Matters – Today is Rare Disease Day 2024

Today, on Rare Disease Day, we’re proud to release a special video featuring researchers from around the globe! Join us as they share why research into rare diseases is vital and how it can make a profound impact on countless lives. Together with the Medical University of Vienna and CeMM we want to raise awareness and foster a community committed to understanding and supporting those with rare conditions. 

Let’s continue to improve rare disease research and emphasize the importance of international collaboration on this day. By pooling our knowledge and resources across borders, we can accelerate discoveries, improve treatments, and ultimately enhance the quality of life for individuals affected by rare diseases worldwide. 

St. Anna CCRI wants to develop new drug against Ewing sarcoma with international partners

A three-year project aims to improve the long-term survival rate of patients with Ewing sarcoma.

(Vienna, 22.02.2024) Ewing sarcoma is a very aggressive, rapidly metastasizing bone cancer. In Austria, five to eight children and adolescents are affected every year. The long-term survival rate is only 50 to 60 percent; those affected who have been diagnosed with metastases and a recurrence of the disease have an even lower statistical chance of survival – of 20 to 30 percent.  It is therefore important to develop complementary medications that significantly increase the chances of recovery after surgery, radiotherapy and chemotherapy and do not place an additional burden on the patient’s body. Until now, the relative rarity of Ewing sarcoma and the lack of preclinical models have been an obstacle to new developments.

HSP90 inhibitors are particularly promising, but none has been approved for clinical use, so far. New HSP90 targeting compounds are now being sought in a binational, three-year project between. St. Anna Children’s Cancer Research Institute (St. Anna – CCRI) and the University of Ljubljana – the research is being funded by the Austrian Science Fund FWF on the Austrian side and the Slovenian Research Agency (ARIS) on the Slovenian side.

Taking the tumor driver out of the game

HSP90 is an essential protein. It supports the correct folding of other proteins so that they can achieve their function. More than 400 proteins benefit from its activity. Among its client proteins there is also the oncogene driving Ewing sarcoma pathogenesis, EWS::FLI1.

The team of Tihomir Tomašič, PhD in Ljubljana is developing novel HSP90 targeting compounds. St. Anna CCRI in Vienna is testing the efficacy and toxicity of these drugs in two innovative models – in the laboratory of Heinrich Kovar, PhD on organoids and in the Innovative Cancer Models group of Martin Distel, PhD on living organisms.

The innovative idea behind the project is that HSP90 inhibitors can take the tumor driver out of the game. To increase targeted efficacy and circumvent unwanted side effects in normal tissues, the teams will test several combination therapies including anti-apoptotic proteins, which are proteins that prevent cell death. 

Research is in the early stages of developing new drugs to combat Ewing sarcoma in the long term. Ultimately, a significant improvement in the survival rate would be a great success.