Research group - Stephan Mielke
Our lab works with translational questions inbetween basic research and clinical care in the field of cell- and gene therapy with a strong focus on cancer.
Although stem cell transplantation has been established over decades, advanced cell-based immunotherapy has recently risen as the fifth pillar of cancer treatment besides surgery, radiotherapy, chemotherapy, and targeted therapy. Remarkably, the development of Chimeric Antigen Receptor (CAR) T-cell therapy has accelerated the field dramatically. However, this is just the beginning of the rise of several new Advanced Therapy Medicinal Products (ATMPs) in cancer care. Most recently, the development of mRNA vaccines against COVID-19 has further sped up the development of new therapies in this field.
Our research group is connected to the JACIE-accredited Medical Department of Cell Therapy and Allogeneic Stem Cell Transplantation in Huddinge (ME CAST). This is part of an even larger USVE (Universitetssjukvårdsenhet) at Karolinska University Hospital which covers the areas GMP production, oligonucleotide therapy, and exosomes. We are closely connected to SWECARNET, Sweden’s CAR T cell competence network and Karolinska’s developing ATMP center.
The following projects are part of our research:
Project 1: Elucidating mechanisms behind the effect, toxicity, and resistance of CAR-T cell therapy.
Project 2: Hospital-based ATMP production in cancer care.
Project 3: Harnessing and redirecting immunity against ovarian cancer.
Research group leader
Group members
Selected publications
Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination.
Gao Y, Cai C, Wullimann D, Niessl J, Rivera-Ballesteros O, Chen P, Lange J, Cuapio A, Blennow O, Hansson L, Mielke S, Nowak P, Vesterbacka J, Akber M, Perez-Potti A, Sekine T, Müller TR, Boulouis C, Kammann T, Parrot T, Muvva JR, Sobkowiak M, Healy K, Bogdanovic G, Muschiol S, Söderdahl G, Österborg A, Hellgren F, Grifoni A, Weiskopf D, Sette A, Loré K, Sällberg Chen M, Ljungman P, Sandberg JK, Smith CIE, Bergman P, Ljunggren HG, Aleman S, Buggert M
Immunity 2022 Sep;55(9):1732-1746.e5
Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study.
Abramson JS, Solomon SR, Arnason JE, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers PGNJ, Hernandez-Ilizaliturri FJ, Izutsu K, Morschhauser F, Lunning MA, Crotta A, Montheard S, Previtali A, Ogasawara K, Kamdar M
Blood 2022 Dec;():
Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial.
Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS,
Lancet 2022 Jun;399(10343):2294-2308
Long-term safety for patients with tisagenlecleucel-treated relapsed/refractory diffuse large B-cell lymphoma.
Jaeger U, Tam CS, Borchmann P, McGuirk JP, Johansen M, Waller EK, Jaglowski S, Andreadis C, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Salles G, Schuster SJ, He F, Maziarz RT, Mayer S, Makita S, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Goto H, Colicino S, Agarwal A, Lobetti-Bodoni C, Bishop MR
Blood Adv 2022 Aug;6(16):4816-4820
Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).
Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, Chabannon C, Ciceri F, Corbacioglu S, Ellard R, Sanchez-Guijo F, Jäger U, Hildebrandt M, Hudecek M, Kersten MJ, Köhl U, Kuball J, Mielke S, Mohty M, Murray J, Nagler A, Rees J, Rioufol C, Saccardi R, Snowden JA, Styczynski J, Subklewe M, Thieblemont C, Topp M, Ispizua ÁU, Chen D, Vrhovac R, Gribben JG, Kröger N, Einsele H, Yakoub-Agha I
Ann Oncol 2022 Mar;33(3):259-275
Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study.
Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT
Lancet Oncol 2021 Oct;22(10):1403-1415
Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group.
Spanjaart AM, Ljungman P, de La Camara R, Tridello G, Ortiz-Maldonado V, Urbano-Ispizua A, Barba P, Kwon M, Caballero D, Sesques P, Bachy E, Di Blasi R, Thieblemont C, Calkoen F, Mutsaers P, Maertens J, Giannoni L, Nicholson E, Collin M, Vaz CP, Metafuni E, Martinez-Lopez J, Dignan FL, Ribera JM, Nagler A, Folber F, Sanderson R, Bloor A, Ciceri F, Knelange N, Ayuk F, Kroger N, Kersten MJ, Mielke S
Leukemia 2021 Dec;35(12):3585-3588
Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial.
Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Chen P, Söderdahl G, Österborg A, Smith CIE, Wullimann D, Vesterbacka J, Lindgren G, Blixt L, Friman G, Wahren-Borgström E, Nordlander A, Gomez AC, Akber M, Valentini D, Norlin AC, Thalme A, Bogdanovic G, Muschiol S, Nilsson P, Hober S, Loré K, Chen MS, Buggert M, Ljunggren HG, Ljungman P, Aleman S,
EBioMedicine 2021 Dec;74():103705
Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells.
Shaim H, Shanley M, Basar R, Daher M, Gumin J, Zamler DB, Uprety N, Wang F, Huang Y, Gabrusiewicz K, Miao Q, Dou J, Alsuliman A, Kerbauy LN, Acharya S, Mohanty V, Mendt M, Li S, Lu J, Wei J, Fowlkes NW, Gokdemir E, Ensley EL, Kaplan M, Kassab C, Li L, Ozcan G, Banerjee PP, Shen Y, Gilbert AL, Jones CM, Bdiwi M, Nunez-Cortes AK, Liu E, Yu J, Imahashi N, Muniz-Feliciano L, Li Y, Hu J, Draetta G, Marin D, Yu D, Mielke S, Eyrich M, Champlin RE, Chen K, Lang FF, Shpall EJ, Heimberger AB, Rezvani K
J Clin Invest 2021 Jul;131(14):
ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia.
Roy DC, Walker I, Maertens J, Lewalle P, Olavarria E, Selleslag D, Lachance S, Buyse M, Wang K, Rovers J, Santi I, Bonig H, Sandler A, Velthuis J, Mielke S
Leukemia 2020 Jul;34(7):1907-1923
Donor-cell leukemia with novel genetic features 2 years after sex-mismatched T cell-depleted haploidentical stem cell transplantation.
Luber V, Lutz M, Thiede C, Haferlach C, Dürk HA, Einsele H, Grigoleit GU, Mielke S
Ann Hematol 2020 Apr;99(4):899-901
Inflammation-induced tissue damage mimicking GvHD in human skin models as test-platform for immunotherapeutics.
Wallstabe J, Bussemer L, Groeber-Becker F, Freund L, Alb M, Dragan M, Waaga-Gasser AM, Jakubietz R, Kneitz H, Rosenwald A, Rebhan S, Walles H, Mielke S
ALTEX 2020 ;37(3):429-440
Large-scale GMP-compliant CRISPR-Cas9-mediated deletion of the glucocorticoid receptor in multivirus-specific T cells.
Basar R, Daher M, Uprety N, Gokdemir E, Alsuliman A, Ensley E, Ozcan G, Mendt M, Hernandez Sanabria M, Kerbauy LN, Nunez Cortes AK, Li L, Banerjee PP, Muniz-Feliciano L, Acharya S, Fowlkes NW, Lu J, Li S, Mielke S, Kaplan M, Nandivada V, Bdaiwi M, Kontoyiannis AD, Li Y, Liu E, Ang S, Marin D, Brunetti L, Gundry MC, Turk R, Schubert MS, Rettig GR, McNeill MS, Kurgan G, Behlke MA, Champlin R, Shpall EJ, Rezvani K
Blood Adv 2020 Jul;4(14):3357-3367
Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial.
Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Reményi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stölzel F, Schetelig J, Junghanß C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Micò MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socié G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, Markiewicz M
Lancet Haematol 2020 Jan;7(1):e28-e39
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT,
N Engl J Med 2019 Jan;380(1):45-56