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Evren Alici group

The Cell and Gene Therapy Group (CGTG) has a particular interest in exploring natural killer (NK) cells in patients with multiple myeloma (MM).

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Evren Alici research group

MM is a malignant neoplasm characterized by clonal proliferation of plasma cells in the bone marrow accounting for 2% of all cancer deaths and nearly 20% of deaths caused by hematological malignancies. The standard treatment for MM is high-dose chemotherapy conditioning with autologous stem cell transplantation (SCT) and immunomodulatory drugs (IMiD), proteasome inhibitors (PIs) as well as monoclonal antibodies (mAbs). Although recent developments in therapies significantly improve the median overall survival (OS), the disease remains incurable due to the persistence of minimal residual disease. Novel modalities complementing or enhancing current treatment options are needed.

Our group’s primary research focus is to optimize and clinically adapt genetic modification strategies to retarget NK cells to tumors with limited off-target effects and toxicity profiles. For this purpose, our group, in collaboration with Hareth Nahi’s group, is currently performing clinical trials where NK cell responses are boosted against malignant MM cells. In our most recent clinical trial, autologous expanded NK cells were infused to six patients at relapse, five of which were still in remission almost four years after the first infusion. The samples collected from this trial are currently analyzed by our group with flow cytometry panels and functional assays that we have developed in-house. The patients’ outcomes, as well as the preliminary results from the cell and cytokine analyses, have motivated us to pursue this in a phase II clinical trial. 

Our projects include generation and testing of genetically engineered NK cells, including chimeric receptor and CAR-NK cells against multiple target antigens. We are exploring the use of small molecules and oncolytic viruses to increase NK cell reactivity against tumor cells in vivo and in vitro. In parallel, we are customizing plasmids and viral vectors for optimal gene transfer into immune cells. 
 

Main current funding

  • Cancerföreningen 
  • VINNOVA (Main PI: H-G Ljunggren)
  • Morphogenesis, Inc.
  • MERCK 
  • Vycellix, Inc. 
  • Sanofi 

Members

Evren Alici

MD, PhD, Group Leader

Evren Alici is a senior scientist and the group leader of the Cell and Gene Therapy Group, HERM, Department of Medicine, Karolinska Institutet. Evren received his MD at Ege University in 1999 and received his PhD from Karolinska Institutet in 2006. Evren's main research interests are natural killer cells, multiple myeloma, lentiviral and retroviral gene transfer, stem cell transplantation and immunology. 

Carin Dahlberg

PhD, Project Coordinator

Carin defended her PhD thesis in Immunology in March 2015 at the Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet. After her PhD, she had a postdoctoral fellowship at Nova Southeastern University in Fort Lauderdale, FL, USA for two years focusing on NK cell therapy for Multiple Myeloma. Since March 2017 Carin has been working in Evren Alici’s group as a Project Coordinator, responsible for ongoing projects as well as setting up new collaborations. 

Alamdar Hussain

M.Sc., PhD, Postdoc

Alamdar received his PhD degree in Molecular Medicine from Karolinska Institutet in the summer of 2013 and worked as an Assistant Professor at CIIT, Pakistan from 2013 until the spring of 2017. Alamdar joined the Evren Alici lab as a Postdoc in April 2017. His research interests include the generation and modification of retro and lenti viral vectors and chimeric receptors for cancer immunotherapy.

Arnika Kathleen Wagner

PhD, Assistant Professor

Arnika received her M.Sc. in 2008 from the University of Lübeck, Germany. She conducted her PhD studies under the supervision of Klas Kärre at the Dept of Microbiology, Tumor and Cell Biology, Karolinska Institutet. Her research focused on NK cells in mouse models for immunotherapy, and studied the crosstalk of NK cells with other immune cells. In Sept 2016, Arnika joined Evren Alici’s group at the Dept of Medicine Huddinge, Karolinska Institutet, to study NK cells in immunotherapy in Multiple Myeloma. Arnika is particularly interested in advancing the use of genetically modified NK cells in different immunotherapeutical approaches.

Dara Mohammad

M.Sc., PhD, Postdoc

Dara received his PhD degree in Molecular Medicine from Karolinska Institutet in 2015 under the supervision of Professor CIE Edvard Smith. He then worked as a postdoctoral research scientist at Evox Therapeutics within Karolinska Institute until May 2018. Dara joined Evren Alici’s group as a postdoctoral research scientist in June 2018. Dara’s research interests include Immuno-cell signaling, cancer development and signal transduction of engineered Extracellular Vesicles (EVs) targeting diseases for cancer immunotherapy application.

Ceyda Çalışkan

M.Sc., PhD, Postdoc

Ceyda received her PhD in Medical Biology and Genetics from Dokuz Eylul University, Turkey in 2016. Ceyda joined Ayten Nalbant's Lab as a Postdoc and worked in a government funded project for one year. Her research focused mainly on Th17 cells and apoptotic mechanisms. In November 2018, she joined the Evren Alici lab and now focuses on gene editing of NK cells for a better cancer treatment.

Michael Chrobok

M.Sc., PhD

Michael received his B.Sc. degree in Biochemistry from Leibniz University Hannover and M.Sc. in Molecular Life Sciences from the University of Hamburg. After finishing his master’s project on the influence of cytomegalovirus on the human immune system at the Heinrich-Pette Institute in Hamburg, Michael started as a PhD student in Evren Alici´s lab at the Karolinska Institute in January of 2013 and defended his thesis “Natural Killer Cells, Multiple Myeloma, and Daratumumab – A Love-Hate Relationship” in May (2019).

Katharina Helene Susek

MD, PhD student

After receiving her medical degree from the University of Muenster, Germany in winter 2014, Katharina was working as a physician in the Department of Radiation Oncology, University Hospital Muenster from January 2015 until December 2017. She joined Evren Alici’s group in January 2018 as a PhD student. Her research focus is the genetic modification of Natural Killer Cells to re-target immune checkpoint inhibition in Multiple Myeloma and herpes-simplex virus type 1 oncolytic virotherapy in the context of Multiple Myeloma and sarcoma.

Maria Karvouni

M.Sc., PhD student

Maria received her diploma in Pharmacy from the University of Athens, Greece, in 2014 and her M.Sc. in Stratified Medicine and Pharmacological Innovation from the University of Glasgow, UK, in 2016. In 2017, she joined Evren Alici's group as a student of the Advanced course in Immune, Infection and Tumour Biology offered by Karolinska Institutet. She is now working as a PhD student in the group. Her research focuses on CAR-NK cells, antibody-drug conjugates (ADCs) and functionalized spider silk for treatment of Multiple Myeloma.

Mari Gilljam

Biomedical Analyst (BMA)

Biomedical analyst in Evren Alici´s group. Educated in GMP work. Developed a closed system for expansion of NK-cells. Worked in GMP facility producing NK-cells in a clinical trial, phase one. Primarily working with cells, both primary and cell lines.

Ann Wallblom

Biomedical Analyst (BMA)    

Ann’s work involves bio banking (taking care of myeloma bone marrow and blood samples), cytogenetics (FISH analyses of myeloma cells) and culturing of NK cells. Results are included in various clinical trials.

Stephan Meinke

PhD, Assistant Professor

One part of Stephan’s research is the investigation of immune-phenotypes of different individuals. He is interested in the changes in different populations of immune cells between healthy donors and patients, as well as in patients in response to different treatments. The other part of his research is transfusion immunology with a focus on antibody-mediated anti-platelet responses. Here, Stephan investigates an approach to generate suitable platelet products for anti-HLA immunised patients by removing HLA molecules from non-matched donor platelets. This work is in collaboration with professor Petter Höglund

Kelly Grahn

Research Group Administrator

Kelly has a BA in Interdisciplinary Studies from the University of British Columbia (UBC), Vancouver, Canada. Kelly has many years of professional international Regulatory Affairs and Quality Systems experience from the Medtech industry. After an inspiring course in Global Health, which had a focus on the United Nations Sustainable Development Goals, Kelly joined the Alici group in January 2018 as a Research Group Administrator. Kelly thrives when working in a collaborative international environment, while contributing to the improvement of people’s lives.

Associated People

Hareth Nahi, Associate Prof, Karolinska University Hospital

Gösta Gahrton, Prof Emeritus, KI

Andreas Lundqvist, Associate Prof, KI

Carina Modin, research nurse, Karolinska University Hospital

Sofia Johansson, Senior Researcher, KI

Stephan Meinke, Assistant professor, KI

Magda-Liz Torres, PhD student (Supervisor: Lisa Westerberg), KI

Charlotte Gran, PhD student (Supervisor: Hareth Nahi), KI

Göran Wålinder, PhD student (Supervisor: Hareth Nahi), KI

Thuy Luu Thanh‎, PhD student (Supervisor: Petter Höglund), KI

Alumni

Tolga Sütlü, PhD. Dissertation 2012: Expansion and genetic modification of human natural killer cells for adoptive immunotherapy of cancer. Opponent: Prof. Jeffrey S. Miller, University of Minnessota. Dr Sutlu left the lab for to do a postdoc at Sabanci University, Turkey. Dr Sutlu is now Assistant Professor at Sabanci University, Turkey.

Adil D. Duru, postdoc. Left the lab 2014 for a senior staff scientist position at Vaccine and Gene Therapy Institute, Florida, USA. Dr Duru is now Assistant Professor at Cell Therapy Institute, Nova Southeastern University, Florida, USA.

Johan Lund, MD PhD (co-supervisor). Dissertation 2016: Clinical studies in multiple myeloma. Opponent: Prof. Frits van Rhee, University of Arkansas for Medical Sciences. Dr Lund is now a hematology specialist and post doc in our group.

Katarina Uttervall, MD PhD (co-supervisor). Dissertation 2015: Biological markers and treatment as prognostic factors in multiple myeloma. Opponent: Prof. Ola Landgren, Memorial Sloan Kettering Cancer Center. Dr Uttervall is now working as an MD and is a post doc in our group.

Selected publications

Comparison between procaine and isocarboxazid metabolism in vitro by a liver microsomal amidase-esterase.[Biochemical studies on camomile components/III. In vitro studies about the antipeptic activity of (--)-alpha-bisabolol (author's transl)].
Moroi K, Sato T, Isaac O, Thiemer K
Biochem. Pharmacol.Arzneimittelforschung 19751975 AugSep;2425(169):1517-211352-4

A combination regimen of bortezomib, cyclophosphamide and betamethasone gives quicker, better and more durable response than VAD/CyBet regimens: results from a Swedish retrospective analysis.
Uttervall K, Admasie J, Alici E, Lund J, Liwing J, Aschan J, et al Acta Haematol. 2013 ;130(1):7-15

Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: implications for gene therapy.
Sutlu T, Nyström S, Gilljam M, Stellan B, Applequist SE, Alici E
Hum. Gene Ther. 2012 Oct;23(10):1090-100

Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study.
Jungebluth P, Alici E, Baiguera S, Blomberg P, Bozóky B, Crowley C, et al
Lancet 2011 12;378(9808):1997-2004

Ex vivo expansion of natural killer cells: a question of function.
Sutlu T, Alici E
Cytotherapy 2011 Jul;13(6):767-8

Clinical impact of chromosomal aberrations in multiple myeloma.
Nahi H, Sutlu T, Jansson M, Alici E, Gahrton G
J. Intern. Med. 2011 Feb;269(2):137-47

IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers.
Alici E
Curr. Opin. Mol. Ther. 2010 Dec;12(6):724-33

GMP facilities for manufacturing of advanced therapy medicinal products for clinical trials: an overview for clinical researchers.
Alici E, Blomberg P
Curr Gene Ther 2010 Dec;10(6):508-15

Clinical-grade, large-scale, feeder-free expansion of highly active human natural killer cells for adoptive immunotherapy using an automated bioreactor.
Sutlu T, Stellan B, Gilljam M, Quezada HC, Nahi H, Gahrton G, et al
Cytotherapy 2010 Dec;12(8):1044-55

Suicide gene therapy for graft-versus-host disease.
Georgoudaki AM, Sutlu T, Alici E
Immunotherapy 2010 Jul;2(4):521-37