Evren Alici group - Cell and Gene Therapy

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

Evren Alici and The Cell and Gene Therapy Group (CGTG). Photo: Emma Karlsson

About our research

Our group’s primary research focus is to optimize and clinically adapt strategies to retarget NK cells to tumors with limited off-target effects and toxicity profiles. For this purpose, we are currently performing clinical trials where NK cell responses are enhanced and retargeted against tumor cells in patients with MM. More specifically, we aim to develop novel NK cell-based therapies including next-generation engagers, next-generation chimeric antigen receptors for NK cells (CAR-NK), and next-generation small molecules for NK cell modulation. Our mission is to shorten production time, increasing target cell specificity, and eliminating unwanted side effects of current cell-based immunotherapies. The product candidates are developed in our translational research laboratories and tested in the clinic, alone and/or in combination with select existing therapeutics (e.g., antibodies, bispecific engagers, small molecules). 

Multiple myeloma (MM)

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.

Projects

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. 

Group leader

Evren Alici

Principal researcher
Alici
H7 Department of Medicine, Huddinge

Evren Alici 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. 

Group members

Sophia Borate

Postdoctoral researcher

Sophia completed her PhD in Biotechnology from the National Centre for Cell Science, India in April 2019. Sophia’s PhD research focus was on generation, in-depth characterization and differentiation of hiPSCs (human induced pluripotent stem cells) from adult stem cells. After completing her PhD, she worked on developing 3D human skin equivalents in vitro for a CRO- Jai Research Foundation, Vapi, India. 

In July 2022, Sophia joined Evren Alici's group as a Postdoctoral researcher. Sophia's main research interests include developing iPSC (induced pluripotent stem cell) lines from blood cells and working on iPSC derived NK cells in vitro. 

Nutsa Burduli

PhD student
Alici
H7 Department of Medicine, Huddinge

Nutsa Burduli joined the Evren Alici group in April 2020 where she is working on NK cell-based immunotherapies in Multiple Myeloma.

She completed her Bachelor’s and Master’s studies at National University of Ireland, Galway where she was first introduced to the area of NK cell research.

Nutsa has previously worked on genetic modifications in NK cells to treat pancreatic cancer.

Carin Dahlberg

Project coordinator
Alici
H7 Department of Medicine, Huddinge

Carin Dahlberg has been working in Evren Alici’s group as a Project Coordinator since March 2017. She is responsible for ongoing projects as well as setting up new collaborations. 

Carin defended her PhD thesis in Immunology in March 2015 at the Department of Microbiology, Tumor and Cell Biology (MTC). 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.

Mari Gilljam

Biomedical scientist
Alici
H7 Department of Medicine, Huddinge

Mari Gilljam is a Biomedical analyst (BMA) in Evren Alici's group, primarily working with cells, both primary and cell lines.

She is educated in GMP work and has developed a closed system for expansion of NK-cells. Mari has worked in a GMP facility producing NK-cells in a clinical trial, phase one.

Kelly Grahn

Project coordinator
Alici
H7 Department of Medicine, Huddinge

Kelly Grahn is the Research Group Coordinator in the Evren Alici group.

She has many years of professional international Regulatory Affairs and Quality Systems experience from the Medtech industry. After an inspiring course in Global Health, with a focus on the United Nations Sustainable Development Goals, Kelly joined the Evren Alici group in January 2018.

Kelly has a BA in Interdisciplinary Studies from the University of British Columbia (UBC), Vancouver, Canada.

Alamdar Hussain

Research Specialist
Alici
H7 Department of Medicine, Huddinge

Alamdar Hussain is a Senior lab manager and 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.

Alamdar received his PhD degree in Molecular Medicine from Karolinska Institutet in 2013. He worked as an Assistant Professor at CIIT, Pakistan between 2013- 2017. 

Charlotte Hållstrand

Biomedical scientist
Alici
H7 Department of Medicine, Huddinge

Charlotte Hållstrand has a Bachelor of Science in Medical Laboratory Technology. Prior to her role as Biomedical Scientist in the Evren Alici group, Charlotte worked at Vecura, KCC, Karolinska University Hospital, starting 1996. At Vecura she mostly worked with GMP production of cell and gene therapy products for clinical trials. 

Maria Karvouni

PhD student
Alici
H7 Department of Medicine, Huddinge

Maria Karvouni first joined Evren Alici's group as a student of the Advanced course in Immune, Infection and Tumour Biology offered by Karolinska Institutet in 2017. Her research focuses on CAR-NK cells, antibody-drug conjugates (ADCs) and functionalized spider silk for treatment of Multiple Myeloma.

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.

 

Kyra Kuhnigk

PhD student
Alici
H7 Department of Medicine, Huddinge

Kyra Kuhnigk joined Evren Alici's group as a PhD student in August 2020. Her research focuses on the killing dynamics and immune synapse formation of genetically modified NK cells. This work is carried out in collaboration with Björn Önfelt (SciLifeLab) at Karolinska Institutet.

Kyra received her M.Sc. in Molecular Life Sciences in 2019 from the University of Lübeck, Germany. 

 

Stephan Meinke

Research Specialist
Höglund
H7 Department of Medicine, Huddinge

One part of Stephan Meinke'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 at MedH, KI.

DARA MOHAMMAD

Researcher
Alici
H7 Department of Medicine, Huddinge

Dara Mohammad joined Evren Alici’s group as a Postdoctoral Research Scientist in June 2018 and became a Researcher in September 2020. Dara’s research interests include Immuno-cell signaling, cancer development and signal transduction of engineered Extracellular Vesicles (EVs) targeting diseases for cancer immunotherapy application.

Dara received his PhD degree in Molecular Medicine from Karolinska Institutet in 2015 under the supervision of Professor C.I. Edvard Smith. He then worked as a postdoctoral research scientist at Evox Therapeutics within Karolinska Institutet until May 2018.

Anders Norman

Research engineer
Alici
H7 Department of Medicine, Huddinge

Anders Norman received his M.Sc.Eng in Medical Biotechnology from KTH Royal Institute of Technology in 2018. His degree project was on the Recombination Enhancer in Kluyveromyces lactis, at the Department of Molecular Biosciences at Stockholm University. After that, Anders worked at a startup company in Solna where he developed cancer diagnostics based on Circulating Tumor Cells in liquid biopsies.

Hazel Reilly

PhD student
Alici
H7 Department of Medicine, Huddinge

Hazel Reilly joined the Evren Alici group in November 2021 where she is working on tumour retargeted iPSC derived NK cells.

Hazel received her B.Sc. degree in Biomedical Science, from Technological University Dublin, in June 2020. She has previously worked on GMP manufacture of hESC derived RPE to treat dry age related macular degeneration.

Alici
H7 Department of Medicine, Huddinge

Katharina Helene Susek 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.

After receiving her medical degree from the University of Muenster, Germany in winter 2014, Katharina worked as a physician at the Department of Radiation Oncology, University Hospital Muenster from January 2015 until December 2017. 

Arnika Kathleen Wagner

Assistant professor
Alici
H7 Department of Medicine, Huddinge

Arnika Wagner joined Evren Alici’s group in September 2016 to study NK cells in immunotherapy in Multiple Myeloma. She is particularly interested in advancing the use of genetically modified NK cells in different immunotherapeutical approaches.

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.

Research Assistants

Didem Cakirsoy

Research assistant
Alici
H7 Department of Medicine, Huddinge

Claire Marsal

Research assistant
Alici
H7 Department of Medicine, Huddinge

Affiliated members

Michael Chrobok

Affiliated to research
H7 Department of Medicine, Huddinge

Susan Dunne

Senior scientist (Avectas)
H7 Department of Medicine, Huddinge

Gösta Gahrton

Affiliated to research
H7 Department of Medicine, Huddinge

Hareth Nahi

Affiliated to research
H7 Department of Medicine, Huddinge

Andreas Lundqvist

Principal researcher
K7 Department of Oncology-Pathology

Ann Wallblom

Biomedical scientist
H7 Department of Medicine, Huddinge

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 Minnesota. Dr Sutlu left the lab for to do a postdoc at Sabanci University, Turkey. Dr Sütlü 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.

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.

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.

Ceyda Çalışkan, Postdoc. Ceyda visited our lab from November 2018 until November 2019.

Thuy Luu Thanh, PhD (co-supervisor). Dissertation 2020: Interleukin 15 throughout murine natural killer cell biology. 

Charlotte Gran, PhD (co-supervisor). Dissertation 2021: Strategies to assess and improve prognostication of plasma cell disorders.

Göran Wålinder, MD PhD (co-supervisor). Dissertation 2022: Plasma cell malignancies in Sweden: Subgroup descriptions and regional outcomes for multiple myeloma. Dr Wålinder is now working as an MD.

Nerges Winblad, PhD (co-supervisor). Dissertation 2022: Exploring early development and regenerative medicine using CRISPR/Cas9.

Research support

  • Cancerföreningen                                                         
  • VINNOVA (Main PI: H-G Ljunggren)
  • Vycellix, Inc. 
  • Vygen-Bio, Inc. 
  • Zelluna Immunotherapy AS
  • Oncternal Therapeutics
  • Avectas
  • Sorrento Therapeutics, Inc.
  • Karolinska Institutet (KID)
  • KI Fonder (Arnika Wagner & Alamdar Hussain)
  • KI Foundation for Virus Research (Katharina Susek)
  • CIMED (Arnika Wagner)
  • Castenbäcks Stiftelsen

Selected publications

  1. 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 1975 AugSep;2425(169):1517-211352-4
  2. 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 alActa Haematol. 2013;130(1):7-15
  3. 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 EHum. Gene Ther. 2012 Oct;23(10):1090-100
  4. 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 alLancet 2011 12;378(9808):1997-2004
  5. Ex vivo expansion of natural killer cells: a question of function.
    Sutlu T, Alici ECytotherapy 2011 Jul;13(6):767-8
  6. Clinical impact of chromosomal aberrations in multiple myeloma.
    Nahi H, Sutlu T, Jansson M, Alici E, Gahrton J. Intern. Med. 2011 Feb;269(2):137-47
  7. 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
  8. 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
  9. 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
  10. Suicide gene therapy for graft-versus-host disease.
    Georgoudaki AM, Sutlu T, Alici EImmunotherapy 2010 Jul;2(4):521-37
28-11-2022
Evren Alici