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Group Roger Olofsson Bagge

Research summary

Our group focus on translational research, bringing new treatments to patients through novel clinical trials. The focus is primarily on breast cancer and malignant melanoma, and we work broadly from clinical trials, aspects on quality of life, immunology and extra-cellular vesicles.

One example of a current project is the Nivo-ILP trial:

Approximately 5-10% of patients with recurrence of malignant melanoma develop lymphatic dissemination manifested as in-transit metastasis. The most effective treatment is isolated limb perfusion (ILP) with a complete response rate of approximately 60%. During ILP the vasculature of an extremity with tumours is isolated and connected to a heart-lung machine which allows perfusion of the limb with very high doses of the alkylating chemotherapeutic agent melphalan.

This treatment avoids systemic side effects, including toxic effects to the cells of the immune system, while giving a very high regional response rate. Avoiding toxicity to immune cells may be a significant benefit since tumours often decrease gradually during several months after a single ILP treatment.

This clinical observation led to our original hypothesis that the anti-tumoural effect is in part caused by immune-mediated mechanisms. We have shown that ILP causes an up-regulation of tumour specific T-cells, however we have also shown this immunological activation is halted by an up-regulation of PD-1.

Aims of the research

The overall aim is to further expand our knowledge concerning the immunological effects of ILP within a clinical trial combining ILP with a PD-1 inhibitor. We will also use this trial as the framework for a translational project analysing tumour biopsies and blood with methods including advanced patient derived xenograft mouse models, FACS of blood and tumour and multi-colour microscopy techniques.

Figure 1. The specific aims of the NivoILP trial.


The specific aims of this study are:

  1. To determine in a clinical trial whether ILP in combination with the checkpoint inhibitor nivolumab significantly increases the complete response rates in melanoma patients with in-transit metastasis.

    In previous studies, we have elucidated the immunogenic effects of ILP and have shown that exposure of melanoma cells to melphalan gives rise to an immunogenic type of cell death that triggers dendritic cells and subsequent T cell activation. However, we have also found that the initial stimulation of the immune system triggers an upregulation of PD-1 on activated T cells.

    These findings serve as the foundation for the clinical trial “Nivo-ILP” aiming to determine whether the anti-PD-1 immune-checkpoint inhibitor nivolumab can improve the efficacy of ILP treatment even further. The trial is designed as a double-blinded placebo-controlled randomized phase Ib/II trial with complete response rate as the primary endpoint.
     
  2. To develop an immune-humanized patient derived xenograft (PDXs) platform from patients with in-transit metastases.

    We will utilise our clinical trial to create patient derived xenograft models (PDXs) from the samples. We have already developed a new immune-humanized PDX model, termed PDXv2.0 where we have been able to show that the model can predict response to adoptive T cell transfer.

    By using the clinical trial as a framework, we will now be able to build a large PDX platform of in-transit metastases, giving us the unique opportunity to further elucidate the immunological effects of ILP and also mimic the trial in a mouse co-clinical trial.

Current group members

Roger Olofsson Bagge, Associate professor, Senior consultant surgeon and group leader at Sahlgrenska Cancer Center.
Karin Ekström, Senior researcher
Rossella Crescitelli, Senior researcher
Junko Johansson, Associate Researcher
Dimitrios Katsarelias, Postdoc
Jenny Heiman Ullmark, PhD student
Nushin Mirzaei, PhD student
Lida Pistioli, PhD student
Hafsteinn Petursson, PhD student
Marina Modin, Research nurse
Therese Bengtsson, Clinical research coordinator
Maria Magnusson, Clinical research nurse

Selected recent publications

  1. A Population-Based Comparison of the AJCC 7th and AJCC 8th Editions for Patients Diagnosed with Stage III Cutaneous Malignant Melanoma in Sweden.
    Isaksson K, Katsarelias D, Mikiver R, Carneiro A, Ny L, Olofsson Bagge R. Ann Surg Oncol. 2019 May 20.
     
  2. Minimally invasive isolated limb perfusion - technical details and initial outcome of a new treatment method for limb malignancies.
    Olofsson Bagge R, Carlson P, Razzazian R, Hansson C, Hjärpe A, Mattsson J, Katsarelias D. Int J Hyperthermia. 2018 Nov 14:1-7
     
  3. Isolated limb perfusion with melphalan triggers immune activation in melanoma patients.
    Johansson J, Kiffin R, Andersson A, Lindnér P, Naredi P, Olofsson Bagge R, Martner A. Front Oncol. 2018 Dec 3;8:570.
     
  4. Mutational Signature and Transcriptomic Classification Analyses as the Decisive Diagnostic Tools for a Cancer of Unknown Primary.
    Olofsson Bagge R, Akif Demir, Joakim Karlsson, Babak Alaei-Mahabadi, Berglind O. Einarsdottir, Henrik Jespersen Mattias F. Lindberg Andreas Muth, Lisa M. Nilsson Marta Persson Johanna B. Svensson Elin M.V. Söderberg Ronald R. de Krijger Ola Nilsson, Erik Larsson Göran Stenman Jonas A. Nilsson. JCO Precision Oncology 2018 :2, 1-25
     
  5. The Effect of Temperature and Perfusion Time on Response, Toxicity, and Survival in Patients with In-transit Melanoma Metastases Treated with Isolated Limb Perfusion.
    Katsarelias D, Rådbo E, Ben-Shabat I, Mattsson J, Olofsson Bagge R. Ann Surg Oncol. 2018 May 15
     
  6. Adjuvant therapies for malignant melanoma.
    Olofsson Bagge R, Ny L. Br J Surg. 2016 Aug;103(9):1095-6.
     
  7. Long-Term Follow-Up Evaluation of 68 Patients with Uveal Melanoma Liver Metastases Treated with Isolated Hepatic Perfusion.
    Ben-Shabat I, Belgrano V, Ny L, Nilsson J, Lindnér P, Olofsson Bagge R. Ann Surg Oncol. 2016 Apr;23(4):1327-34
     
  8. Clinical response and regional toxicity following isolated limb infusion compared to isolated limb perfusion for in-transit melanoma.
    Dossett L, Ben-Shabat I, Olofsson Bagge R, Zager J. Ann Surg Oncol. 2016 Feb 11.
     
  9. Health-Related Quality of Life for Patients Who have In-Transit Melanoma Metastases Treated with Isolated Limb Perfusion.
    Lindqvist Bagge AS, Ben-Shabat I, Belgrano I, Olofsson Bagge R. Ann Surg Oncol. 2016 Feb 11.
     
  10. Melphalan, anti-melanoma immunity and inflammation.
    Martner A, Johansson J, Ben-Shabat I, Olofsson Bagge R. Cancer Research. 2015 Dec 15;75(24):5398-9
     
  11. Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
    Einarsdottir B, Olofsson Bagge R, Bhadury J, Jespersen H, Mattsson J, Nilsson L, Truvé K, Dávila López M, Naredi P, Nilsson O, Stierner U, Ny L, Nilsson J. Oncotarget. 2014 Oct 30;5(20):9609-18
     
  12. Isolated Hepatic Perfusion for Ocular Melanoma Metastasis - Registry Data Suggests a Survival Benefit.
    Olofsson Bagge R, Cahlin C, All-Ericsson C, Hashimi F, Mattsson J, Rizell M, Lindnér P. Ann Surg Oncol. 2014 Feb;21(2):466-72
     
  13. Melan-A specific CD8+ T lymphocytes after hyperthermic isolated limb perfusion: a pilot study in patients with in-transit metastases of malignant melanoma.
    Olofsson Bagge R, Lindberg E, Karlsson-Parra A, Lindnér P, Mattsson J, Andersson B. Int J Hyperthermia. 2013 May;29(3):234-8.
     


More group Roger Olofsson Bagge publications on PubMed

SATMEG

Read more about the group constellation of SATMEG and its activities.

Contact Information

Roger Olofsson Bagge

E-mail: Roger Olofsson Bagge
Phone: +46 (0)31-342 8207

Visiting address:
Sahlgrenska Center
for Cancer Research,
Medicinaregatan 1F
413 90 Gothenburg

Page Manager: Yael Zukovsky Fitoussi|Last update: 4/1/2020
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