Mattias Carlsten group

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

Research Program 

Assistant Professor Dr. Mattias Carlsten M.D. Ph.D. was recently recruited from National Institutes of Health (NIH), USA, and is currently expanding his translational research group at the Karolinska Institutet. The group is located at HERM, Department of Medicine, Huddinge, Karolinska Institutet. The main research focus of Dr. Carlsten’s 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. As a physician-scientist, sharing his position as research group leader at Karolinska Institutet with his role as a clinician at the Center for Hematology 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.

Members

Mattias CarlstenMattias Carlsten, M.D. Ph.D., Group leader, Assistant Professor

Mattias Carlsten received his M.D. and Ph.D. from Karolinska Institutet, Stockholm, Sweden, and has worked as a 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. His 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 has experience in running clinical trials on adoptive NK cell infusion at both the Karolinska Institute and the NIH, and has been involved in multiple clinical studies of drugs aimed at bolstering tumor cytotoxicity by endogenous NK cells. In addition to research, he is also training to become a specialist in hematology.

Caroline LeijonhufvudCaroline Leijonhufvud, M.D., Ph.D. student

Caroline Leijonhufvud received her M.D. from Karolinska Institutet 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 Karolinska (CCK) in 2013 and did her degree project in medicine 2014/2015 at KI/NIH with Dr. Carlsten. She joined the Carlsten group 2016. Her research focuses on NK cell target 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, Karolinska Institutet, and Richard W. Childs at the NIH. Her Ph.D. is supported by the Clinical Scientist Training Programme (CSTP) at Karolinska Institutet.

 

Filip SegerbergFilip Segerberg, M.D., Ph.D. student

Filip Segerberg received his M.D. from Karolinska Institutet 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. Filip is currently studying homing of NK cells and how this can be modified to redirect their migration to tumor-bearing tissues and thereby further improve NK cell-based cancer immunotherapy. 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.

Melanie LambertMelanie Lambert, PhD, Post-doc

Melanie Lambert received her PhD on new therapies against acute myeloid leukemia (AML) from University of Lille, France, 2018. With her background in AML and xeno-mouse models, her post-doctoral work focuses on modulation of donor lymphocyte infusion (DLI) grafts for improved bone marrow homing with the overall aim of improving graft-versus-leukemia meanwhile reducing the risk of graft-versus-host disease in patients receiving DLI due to post-transplantation leukemia relapse. Her work is supported by Barncancerfonden and Åke Wiberg.

Associated members 

Emily Levy, Biologist, Ph.D. student
Ph.D. student with Richard W. Childs, NIH, co-supervised by Mattias Carlsten. Supported by funding from the NIH and the Dean R. O’Neill Renal Cell Cancer Fund.

John Daly, Biologist, Ph.D. student
Ph.D. student with Michael O’Dwyer, NUI Galway, Ireland, co-supervised by Mattias Carlsten. Supported by funding from the Irish Cancer Society.

Former members

Monika Enqvist (Formerly Simonsson), PhD

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, 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

  • SSMF Stora Anslag
  • Wallenberg Clinical Fellow
  • Jeanssons Stiftelser
  • Radiumhemmetsforskningsfond
  • Barncancerfonden
  • Lars Hiertas Stiftelse
  • Åke Wiberg
  • CSTP (for Caroline Leijonhufvud)
  • CSTP (for Filip Segerberg)
  • CIMED

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.

Open positions 

There are currently no open positions, but please do not hesitate to contact Mattias Carlsten per email if you are interested to contact the group

Cancer geneticsHematologyLeukemiaTransplantation