MRCRM Mini-Symposium 2023

Program

11.00-11.30

Food and mingle

11.30-11.35

Welcome, by MRCRM Centre Leader, Professor Einar K. Kristoffersen

11.35-12.20

MRCRM Keynote lecture: Finding Safe and Effective T Cell Receptors for the Next Generation of Cancer Immunotherapy, by Professor Johanna Olweus

12.20-12.45

CD37 represents a new CAR target for the treatment of acute myeloid leukaemia, by Senior Researcher Pascal Francois Gelebart

12.45-13.00

Coffee break

13.00-13.25

3D cell culture under flow – Mechanical Regulation of Bone Marrow Mesenchymal Stem Cells, by Researcher Shuntaro Yamada

13.25-13.45

Clinical biomaterials: Contributing to improved performance and safety of implants, by Senior Researcher Paul Johan Høl

13:45-13.55

3D diamond groth on medical implants, by PhD student Marit Hougen

13.55-14.05

Tregs in schizophrenia – numbers, function, and the influence of prednisolone, by Resident Physician Hanne Wrengler Velure

14.05-14.15

Induction of pluripotency: a Xeno-free approach, by PhD student Hassan Mohamed Abdel-Raouf Ali 

14.15-14.30

Closing remarks

About the speakers and abstracts

Johanna Olweus, Professor; MD, PhD  

Group leader and principal investigator at Department of Cancer Immunology, Oslo University Hospital (OUS)  

Head of K.G. Jebsen Centre for Cancer Immunotherapy, University of Oslo (UiO) 

Finding Safe and Effective T Cell Receptors for the Next Generation of Cancer Immunotherapy:

T-cell receptors (TCRs) can access a wide array of intracellular antigens currently unavailable to CARs, potentially expanding the repertoire of tumor targets for adoptive cell therapies. Neoantigens encoded by mutations are attractive tumor-specific targets that were recently exploited in autologous TCR T-cell therapies. However, challenges include that the large majority of mutations is unique to the individual patient, that TCRs might not be identified from the patient in time for efficacious treatment, and that TCRs identified from patients might have insufficient avidities. Hence, there is a need for alternative strategies to identify immunogenic targets that are shared among patients, and efficacious TCRs recognizing them. Our group has developed technologies to identify TCRs from healthy donors, circumventing the suppressed immune system of the patient. To this end, we have demonstrated that a TCR recognizing a mutation that is shared among a subgroup of patients with acute myeloid leukemia (AML) can mediate eradication of AML in patient-derived xenograft models, including leukemia cells with cancer stem cell properties. These results show proof-of-concept that TCR-T cells targeting a single, shared neoantigen can eradicate cancer in disease-relevant models (Giannakopoulou et al, Nature Cancer, 2023). Moreover, we recently published a pipeline for pre-clinical selection of safe candidate therapeutic TCRs in vitro (Fôldvari et al, NPJ Vaccines 2023) that will be discussed. 

Pascal Francois Gelebart, PhD 

Senior Researcher, Department of Clinical Science, University of Bergen 

CD37 represents a new CAR target for the treatment of acute myeloid leukaemia:

Acute myeloid leukaemia (AML) represents a peculiar challenge for chimeric antigen receptor (CAR) therapy due to the lack of AML cell surface-specific target. Current CAR therapy presents the risk of toxicity and myeloablation due to the targeting of the hematopoietic stem cells (HSCs). The leukocyte-specific tetraspanin 37 (CD37), which is restrictedly found in mature B cells, was recently documented to be overexpressed in AML. In the present study, we developed a CAR T cell therapy against the CD37 antigen and showed that CD37CAR T cells could specifically kill AML cells, secrete inflammatory cytokines, and control tumour development in several xenograft animal models. In pre-clinical studies, using patient-derived xenograft (PDX) cells, our CD37 CAR T demonstrated a superior ability to control disease recurrence in the bone marrow in comparison to benchmarked CAR construct targeting CD33. In contrast to the CD33 CAR T, the CD37 CAR T  exhibits no toxicity toward healthy bone marrow cells and HSCs. Our work is the first to describe the use of the CD37 antigen for the development of a safer CAR T cell therapy for AML. Our observations support the clinical evaluation of CD37 CAR T cell therapy in AML.   

Shuntaro Yamada, PhD

Researcher at the Tissue Engineering Group, Institute of Clinical Dentistry, University of Bergen 

3D cell culture under flow – Mechanical Regulation of Bone Marrow Mesenchymal Stem Cells:

There is a growing demand for three-dimensional cell culture platforms in tissue engineering and regenerative medicine. In this study, we employed a perfusion bioreactor system with bone marrow-derived mesenchymal stem cells (BMSCs) seeded on synthetic polymer scaffolds and evaluated the mechanical regulation of BMSCs, with a specific focus on osteogenic differentiation. Under perfusion exerting sub-physiological levels of fluid shear stress, BMSCs displayed the osteoblastic phenotype, including upregulation of osteogenic markers and mineralization, in the absence of osteoinductive supplements. Notably, mechanically induced osteogenic differentiation was attributed to induced actomyosin contractility under perfusion. This presentation will provide insight into the utility of perfusion bioreactor systems for cell culture and cellular regulation under fluid flow. 

 
Paul Johan Høl, PhD 

Senior researcher and leader of the Biomatlab, Department of Clinical Medicine, University of Bergen 

Clinical biomaterials: Contributing to improved performance and safety of implants:

Over 25% of European adults aged 65 and older suffer from degenerative joint disease, leading to pain and disability. Elective hip and knee replacement rates are on the rise, nearing 2.5 million procedures annually in OECD countries. However, 12% of these implants are expected to fail within a decade, necessitating revision surgery.

Biomatlab's primary goal is to evaluate joint replacement device performance, driving the development of better treatments. Their Implant Retrieval Center, headed by senior researcher Paul Johan Høl, specializes in studying orthopedic explants and associated biological samples. Their work involves the collection of devices that have either been replaced or fulfilled their intended purpose. Additionally, Biomatlab actively participates in several clinical trials aimed at evaluating the outcomes of novel implants and treatment approaches. Their primary focus revolves around gaining insights into the failures observed in joint replacements, frequently linked to implant loosening and osteolysis, which can be initiated by adverse immune reactions to wear debris. 

Marit Hougen, MSc 

PhD student, Department of Physics and Technology, University of Bergen

3D diamond growth on medical implants:

The PhD project is about coating orthopaedic implants with diamond to improve their biocompatibility and osseointegration. As we know, the implants used today are not ideal, needing revision surgery after 15 years, if not sooner, because of issues like infections or loosening of the implant. Diamond is known for being an exceptional material, but it is also biocompatible and has shown anti-microbial and anti-bacterial properties. Moreover, diamond coatings can be tailored and functionalised to modify cells' responses and could be customised to fit the needs of the patients. As such, coating the implants already used today with diamond could be a solution to the previously mentioned problems. However, the techniques used today to deposit diamond coatings do not enable us to coat complex shapes and geometries. The first part of the PhD project focuses on synthesising diamond coatings on flat surfaces with different surface topography, roughness, and physicochemical properties and studying their effect on cells' behaviour. 

Hanne Wrengler Velure, MD

Resident physician in Division of Psychiatry, Department of Mental Health Research, Haukeland University Hospital

Tregs in schizophrenia – numbers, function, and the influence of prednisolone:

T-regulatory cells (Tregs) are a subset of immune cells, which may be hypofunctional in schizophrenic patients. Hypofunctional Tregs are postulated to imply an astrocyte-microglial imbalance, with links to the neurodevelopmental and neurotransmitter dysfunction that underlie symptoms of schizophrenia. In vitro and animal studies show that treatment with prednisolone may enhance Treg function, and targeting immune disturbances can therefore be a potential new medical intervention for schizophrenia.

The aim of this study is to improve the understanding of the Treg pathology in schizophrenia, and specifically to evaluate how treatment with prednisolone influences the proportions and functions of the Treg system. 

 
Hassan Mohamed Abdel-Raouf Ali, MSc 

PhD student, Tissue Engineering Group, Institute of Clinical Dentistry, University of Bergen

Induction of pluripotency: a Xeno-free approach:

Induced pluripotent stem cells (iPS) have been touted as highly promising in the fields of regenerative medicine/research. However, to facilitate and ensure safe clinical use, iPS generation must be devoid of xenogenic products. This presentation will focus on the assessment of a xeno-free protocol for iPS generation, specifically on how it affects cell reprogramming efficiency, the resultant iPS, and how it compares to mainstream xenogenic protocols.