Arnika Wagner team – Genetic Modification of NK cells for Optimized Functions against Cancer
Our research focuses on the biology of human NK cells and opportunities to optimize their functions in the therapy of cancer
The team as part of the Cell & Gene Therapy Group at the Center for Hematology and Regenerative Medicine (HERM).
The team strives to optimize NK cell functions for cell therapy against cancer. Our 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.
Our main interest is to understand how NK cell functions against cancer can be improved and harnessed in cellular therapy.
NK cells have recently gained attention as a promising tool for cancer immunotherapy. These cells can rapidly kill multiple tumor cells through non-MHC-restrictive effects and can recruit both innate and adaptive immune cells through the secretion of cytokines and chemokines. Equipping NK cells with additional natural or chimeric receptors has been shown to enhance tumor-targeting activity. However, due to their central role in anti-viral defense, NK cells are inherently resistant to any introduction of genetic material. To enable feasible generation of NK cell therapeutic products, we constantly strive to optimize means of genetic modification. Furthermore, we focus on developing novel chimeric receptors that synergize with inherent functions of NK cells for optimal anti-cancer activity. Some of the receptors enhance tumor-targeting and -killing capacity, while others are designed to facilitate NK cell engraftment after infusion, especially when used in combination therapies. In addition, we are interested in molecules that segregate pathways leading to target cell killing from other NK cell functions such as cytokine production, aiming at developing an NK cell product with improved killing capacity of cancer cells.
owards these goals, we combine molecular biology, 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.
Arnika has a long-standing expertise in the field of NK cell research both in human and mice. Her research focuses primarily on NK cells and their use in the therapy of cancer.
Anders received his M.Sc.Eng in Medical Biotechnology from KTH Royal Institute of Technology in 2018.
After working with single-cell DNA sequencing in industry he joined The Cell and Gene Therapy Group in 2020.
He is currently supporting the group with regards to plasmid cloning, CRISPR design, bioinformatics and analysis of large datasets, in addition to being the lab manager for the group's molecular biology lab.
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. She has previously worked on genetic modifications in NK cells to treat pancreatic cancer.
Nutsa is currently working on deciphering genetic cues that are important for NK cell killing and cytokine production capacity, by suing a whole-genome CRISPR perturbation screen.
Previous team members
- Joanna Tsialta, Internship students (January-September 2021)
- Hanna Briesch, Master student (May-September 2021)
- Jason Clochard, Research Assistant (January-November 2022)
- Hendrik Schürer, Visiting Researcher (August 2022-Msarch 2023)
- Anna Pumpe, Master student (March-September 2023)
- KI funding for doctoral education (KID)
- Karolinska Institutets forskningsfonder
- Åke Wibergs Stiftelse
- Åke Olsson Stiftelse
- Vetenskapsrådet (VR)
- European Hematology Association (EHA)
- Autologous NK cells as consolidation therapy following stem cell transplantation in multiple myeloma.
Nahi H, Chrobok M, Meinke S, Gran C, Marquardt N, Afram G, Sutlu T, Gilljam M, Stellan B, Wagner AK, Blomberg P, Holmqvist PH, Walther-Jallow L, Mellström K, Liwing J, Gustafsson C, Månsson R, Klimkowska M, Gahrton G, Lund J, Ljungman P, Ljunggren HG, Alici E
Cell Rep Med 2022 Feb;3(2):100508
- Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products.
Silva DN, Chrobok M, Rovesti G, Healy K, Wagner AK, Maravelia P, Gatto F, Mazza M, Mazzotti L, Lohmann V, Sällberg Chen M, Sällberg M, Buggert M, Pasetto A
Front Immunol 2022 ;13():896242
- Challenges in αCD38-chimeric antigen receptor (CAR)-expressing natural killer (NK) cell-based immunotherapy in multiple myeloma: Harnessing the CD38dim phenotype of cytokine-stimulated NK cells as a strategy to prevent fratricide.
Karvouni M, Vidal-Manrique M, Susek KH, Hussain A, Gilljam M, Zhang Y, Gray JD, Lund J, Kaufmann G, Ljunggren HG, Ji H, Lundqvist A, Wagner AK, Guo W, Alici E
Cytotherapy 2023 Jul;25(7):763-772
- A tractable microscopy- and flow cytometry-based method to measure natural killer cell-mediated killing and infiltration of tumor spheroids.
Schwietzer YA, Susek KH, Chen Z, Alici E, Wagner AK
Methods Cell Biol 2023 ;178():43-61
- Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy.
Susek KH, Schwietzer YA, Karvouni M, Gilljam M, Keszei M, Hussain A, Lund J, Kashif M, Lundqvist A, Ljunggren HG, Nahi H, Wagner AK, Alici E
Cancer Immunol Immunother 2023 May;72(5):1153-1167
- PD-1 expression on mouse intratumoral NK cells and its effects on NK cell phenotype.
Wagner AK, Kadri N, Tibbitt C, van de Ven K, Bagawath-Singh S, Oliinyk D, LeGresley E, Campbell N, Trittel S, Riese P, Ribacke U, Sandalova T, Achour A, Kärre K, Chambers BJ
iScience 2022 Oct;25(10):105137
- Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma.
Nahi H, Chrobok M, Gran C, Lund J, Gruber A, Gahrton G, Ljungman P, Wagner AK, Alici E
PLoS One 2019 ;14(2):e0211927
- IL-15 and CD155 expression regulate LAT expression in murine DNAM1+ NK cells, enhancing their effectors functions.
Luu TT, Wagner AK, Schmied L, Meinke S, Freund JE, Kambayashi T, Ravens I, Achour A, Bernhardt G, Chambers BJ, Höglund P, Kadri N
Eur J Immunol 2020 Apr;50(4):494-504
- Expression of CD226 is associated to but not required for NK cell education.
Wagner AK, Kadri N, Snäll J, Brodin P, Gilfillan S, Colonna M, Bernhardt G, Höglund P, Kärre K, Chambers BJ
Nat Commun 2017 May;8():15627
- Retuning of Mouse NK Cells after Interference with MHC Class I Sensing Adjusts Self-Tolerance but Preserves Anticancer Response.
Wagner AK, Wickström SL, Tallerico R, Salam S, Lakshmikanth T, Brauner H, Höglund P, Carbone E, Johansson MH, Kärre K
Cancer Immunol Res 2016 Feb;4(2):113-23