Cell and Gene Therapy – Evren Alici group

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).

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. We collaborate closely with the Myeloma Group where Evren Alici is currently Acting Principle Investigator.

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. 

Arnika Wagner team 

Genetic Modification of NK cells for Optimized Functions against Cancer

The Wagner team strives to optimize NK cell functions for cell therapy against cancer. The research can be divided into three areas, optimization of NK cell genetic modification, development of novel chimeric receptors for improved tumor-targeting, and dissection of genes important for distinct NK cell functions. The main interest is to understand how NK cell functions against cancer can be improved and harnessed in cellular therapy. Towards these goals, we combine molecular biology, genetic modification, flow cytometry, proliferation and cytotoxicity assays, and CRISPR screening to assess pathways leading to enhanced killing, improved genetic modification and enhanced resistance to immune suppressive cues.  

Our vision is that our generated knowledge will be translated into development and optimization of next-generation NK cell therapy against cancer.  

Publications

Selected publications

Funding

  • Cancerföreningen                                                         
  • VINNOVA (Main PI: H-G Ljunggren)
  • Vycellix, Inc. 
  • Vygen-Bio, Inc. 
  • Oncternal Therapeutics
  • Karolinska Institutet (KID)
  • Castenbäcks Stiftelsen

Members and contact

Group leader

All members of the group

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.

Michael Chrobok, PhD (supervisor). Dissertation 2019: Natural Killer Cells, Multiple Myeloma and Daratumumab - a love-hate relationship.

Susan Dunne, visiting Senior Scientist, 2020-2021.

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.

Maria Karvouni, PhD (supervisor). Dissertation 2023: Cellular and personalized therapies in multiple myeloma with special emphasis on retargeted natural killer cells.