Mattias Carlsten group

Immune cells are powerful tools for targeting cancer cells. By utilizing their intrinsic capacity to identify and eliminate malignant cells combined with new techniques to genetically engineer or by other means modify them, research groups around the world are now studying how immune cells can be modulated to more efficiently target cancer.

Mattias Carlsten Research group
Some of the staff members in Mattias Carlsten Research group

Research Program

With the aim of reducing the use of chemotherapy and radiation and replace these treatment modalities with immunotherapy approaches, the Carlsten group hope to improve both outcomes and quality of life for patients with cancer.

The main research focus for the research group is to study how the immune system can be utilized to treat cancer. More specifically, the group focuses its work around basic biology and genetic engineering of Natural Killer (NK) cells with the overall aim of applying new discoveries in settings of cellular cancer immunotherapy. The group is also focusing on transplantation biology including therapies for patients with post-transplantation leukemia relapse.

The research group is located at HERM, Department of medicine, Huddinge, Karolinska Institutet.

Hör Mattias Carlsten berätta om sin forskning kring ny behandling vid svår leukemi

Group leader

Mattias Carlsten

M.D. Ph.D., Group leader, Assistant Professor

Assistant Professor Dr. Mattias Carlsten received his M.D. and Ph.D. from Karolinska Institutet, Stockholm, Sweden. After working as Post-doc and Staff Scientist with Dr. Richard W Childs at the Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health (NIH), USA, Mattias Carlsten launched his translational research group at the Karolinska Institutet during late 2016.

Mattias' research focuses on natural killer (NK) cell biology and how NK cells can be used for cancer immunotherapy, with a particular focus on translating new findings from the bench to the bedside. He also runs project related to T cell-based therapies. Dr. Carlsten has experience in running clinical trials on adoptive NK cell infusion at both the Karolinska Institutet and the NIH, and has been involved in multiple clinical studies of drugs aimed at bolstering tumor cytotoxicity by endogenous NK cells.

As a physician-scientist, sharing his position as research Group leader at Karolinska Institutet with his role as a clinician (Specialist in Hematology) at the Center for Cell Therapy and Allogeneic Stem Cell Transplantation (CAST) at the Karolinska University Hospital, Dr. Carlsten’s work is stretched from pre-clinical in vitro studies, including bench work and animal models, to early clinical trials involving cellular cancer immunotherapy and immunomodulating drugs

Group members

Caroline Leijonhufvud

M.D., Ph.D. student

Caroline Leijonhufvud received her M.D. from Karolinska Institutet (KI) 2016, after which she worked as a junior doctor in transplantation surgery and stem cells transplantation. Caroline started as a pre-Ph.D. student with Dr. Andreas Lundqvist at Cancer Center at KI  (CCK) in 2013 and did her degree project in medicine 2014/2015 at KI/NIH with Dr. Carlsten. Her Ph.D. projects focus on NK cell targeting specificity before and after ex vivo expansion and how the NK cells can be genetically engineered to further improve their tumor targeting capacity, including antibody-dependent cellular cytotoxicity. Caroline is supervised by Mattias Carlsten and co-supervised by Andreas Lundqvist, CCK, KI, and Richard W. Childs at the NIH. Her Ph.D. is supported by the Clinical Scientist Training Programme (CSTP) at Karolinska Institutet and the Research Medical Internship Programme (forskar-AT) at Stockholm County and KI.

Filip Segerberg

M.D., Ph.D. student

Filip Segerberg received his M.D. from Karolinska Institutet (KI) 2018. During 2016/2017 he did his degree project in medicine in the Carlsten group at KI, where he studied the cytotoxic capacity of NK cells in blood of patients with follicular lymphoma. Since starting his PhD in 2018, Filip’s research is focused on NK cell-based immunotherapy against acute myeloid leukemia (AML). More specifically, Filip is studying how NK cells can be genetically modified in order to improve their bone marrow homing potential and tumor targeting capacity. To gain a better understanding of AML and other hematological diseases, Filip has also worked as a junior doctor in the hematology ward at the Karolinska University Hospital. Besides his interest in research and medicine, Filip also enjoys outdoor activities such as rock climbing and running. Filip is supervised by Mattias Carlsten and co-supervised by Prof. Petter Höglund (also at HERM). His Ph.D. is supported by the Clinical Scientist Training Programme (CSTP) at KI.

Laura Sanz

PhD, Post-doc

Laura Sanz received her PhD on new nanomedicine-based therapeutic applications developed to treat cancer from Universidad Autónoma de Madrid, Spain, 2019. With her background in immune cell homing to the tumor microenvironment, her post-doctoral work focuses on understanding how tumor cells can impair NK cell homing to the bone marrow in acute myeloid leukemia (AML) and how to genetically modified NK cells to overcome this limitation, with the overall aim of optimizing adoptive NK cell infusion. Her work is supported by Barncancerfonden.

Kristina Witt

PhD, Post-doc

Kristina Witt received her Ph.D. from Karolinska Institutet, Stockholm, Sweden in 2019 for her work on Cripto-1, a novel target for cancer immunotherapy. Under supervision of Dr. Andreas Lundqvist and in close collaboration with Prof. Rolf Kiessling (both Department of Oncology-Pathology), she studied the tumor directed immune response after Cripto-1 DNA vaccination in preclinical murine tumor models. She further studied how NK cell activity is impaired by the tumor microenvironment and therapies in solid tumors and investigated to overcome these challenges. Dr. Witt’s research aim is to improve NK cell-based immunotherapies. In January 2020 she joined the Carlsten group and her projects focus on strategies to enhance NK cell persistence in vivo through genetic modification ex vivo.

Agneta Andersson

Biomedical scientist

Agneta works as support in all projects and take care of things that keep the lab up and running, such as taking care of cells, ordering, chemicals and risk assessments.

Caroline Eriksson

Research Assistant

Caroline Eriksson received her MSc and Civil Engineering degrees in Medical Biotechnology in 2020 from KTH Royal Institute of Technology, Stockholm, Sweden. She conducted her Master’s degree project in Prof. Yenan Bryceson laboratory at the Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, where she then also worked as a research assistant before joining the Carlsten group in 2021.

Lisanne Schoutens

Master student

Lisanne Schoutens studied medicine at the University of Cambridge (2011-2014, pre-clinical studies) and University College London (2014-2017, MBBS) and subsequently worked as a junior doctor at Oxford University Hospitals. Her early research experiences included a summer studentship at the Vaccine and Immunotherapy Center at Massachusetts General Hospital, studying density-dependent behavior in cancer cells, and a bachelor’s project at the Department of Immunology in Cambridge. She is currently studying for a master’s degree in biomedicine at Karolinska Institute and has joined the Carlsten lab for her master’s thesis. Her project will focus on the cytotoxic function of NK cells after genetic modification. In the future, Lisanne hopes to combine research with medical specialty training as a haematologist.

Associated members

John Daly

PhD student

Supervised by Michael O’Dwyer, NUI Galway, Ireland, and co-supervised by Mattias Carlsten. Supported by funding from the Irish Cancer Society.

Ida Friberger (former Jonson)

PhD student

Supervised by Thuy Tran, Karolinska institutet, and co-supervised by Staffan Holmin and Mattias Carlsten.

Former members

  • 2018- 2020 Mélanie Lambert, PhD – former Post-doc (Karolinska institutet)
     
  • 2019-2020 Angelique Fokkema – former Master Student (Uppsala University)
     
  • 2020 Anton Olander – former Medical student (Karolinska institutet)
     
  • 2019 Elise Mozin – former Master Student (UTC, France)
     
  • 2014-2019 Emily Levy, Biologist, former PhD student. Received her Ph.D. from George Washingon University with Richard W. Childs (NIH) as main supervisor, co-supervised by Mattias Carlsten and David Allen (NIH).
     
  • 2012-2016 Monika Enqvist (Formerly Simonsson), former PhD student. Received her PhD from the Karolinska Institutet supervised by Karl-Johan Malmberg and co-supervised by Mattias Carlsten and Yenan Bryceson.

Keywords

NK cells, Cancer, Immunotherapy, Cell therapy, Tumor immunology, Genetic engineering, Hematology, Lymphoma, Leukemia, Transplantation

Examples of ongoing collaborations

  • Richard Childs, NIH, USA
  • Andreas Lundqvist, KI
  • Björn Wahlin, KI
  • Michael O’Dwyer, NUIG, Ireland
  • Petter Höglund, KI
  • Yenan Bryceson, KI

Financial support (selected)

  • SSMF Stora Anslag
  • Wallenberg Clinical Fellow
  • Jeanssons Stiftelser
  • Cancerfonden
  • Vetenskapsrådet
  • CIMED
  • CSTP (for Caroline Leijonhufvud)
  • CSTP (for Filip Segerberg)
  • Clas Groschinsky

Selected publications

Checkpoint Inhibition of KIR2D with the Monoclonal Antibody IPH2101 Induces Contraction and Hyporesponsiveness of NK Cells in Patients with Myeloma.
Carlsten M, Korde N, Kotecha R, Reger R, Bor S, Kazandjian D, et al
Clin. Cancer Res. 2016 Nov;22(21):5211-5222.

.Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity CD16 and CCR7 Augments Rituximab-Induced ADCC against Lymphoma and Targets NK Cell Migration toward the Lymph Node-Associated Chemokine CCL19.
Carlsten M, Levy E, Karambelkar A, Li L, Reger R, Berg M, et al
Front Immunol 2016 ;7():105.

.mRNA Transfection to Improve NK Cell Homing to Tumors.
Levy E, Carlsten M, Childs R
Methods Mol. Biol. 2016 ;1441():231-40.

.Coordinated expression of DNAM-1 and LFA-1 in educated NK cells.
Enqvist M, Ask E, Forslund E, Carlsten M, Abrahamsen G, Béziat V, et al
J. Immunol. 2015 May;194(9):4518-27.

.Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications.
Carlsten M, Childs R
Front Immunol 2015 ;6():266.

.The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies.
Dosani T, Carlsten M, Maric I, Landgren O
Blood Cancer J 2015 Jul;5():e321.

.Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens.
Childs R, Carlsten M
Nat Rev Drug Discov 2015 Jul;14(7):487-98.

.A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma.
Korde N, Carlsten M, Lee M, Minter A, Tan E, Kwok M, et al
Haematologica 2014 Jun;99(6):e81-3.

.Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers.
Ito S, Bollard C, Carlsten M, Melenhorst J, Biancotto A, Wang E, et al
Mol. Ther. 2014 Jul;22(7):1388-1395.

.Doxorubicin sensitizes human tumor cells to NK cell- and T-cell-mediated killing by augmented TRAIL receptor signaling.
Wennerberg E, Sarhan D, Carlsten M, Kaminskyy V, D'Arcy P, Zhivotovsky B, et al
Int. J. Cancer 2013 Oct;133(7):1643-52.

.Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes tumor cells to CD94/NKG2A-positive NK cells.
Enqvist M, Nilsonne G, Hammarfjord O, Wallin R, Björkström N, Björnstedt M, et al
J. Immunol. 2011 Oct;187(7):3546-54.

Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome.
Carlsten M, Baumann B, Simonsson M, Jädersten M, Forsblom A, Hammarstedt C, et al
Leukemia 2010 Sep;24(9):1607-16.