eRapport

Off-the-Shelf Cancer Immunotherapy with Adaptive Natural Killer Cells

Prosjekt
Prosjektnummer
2017118
Ansvarlig person
Karl-Johan Malmberg
Institusjon
Oslo universitetssykehus HF
Prosjektkategori
Åpen prosjektstøtte
Helsekategori
Cancer, Inflammatory and Immune System
Forskningsaktivitet
5. Treatment Developement
Rapporter
2020 - sluttrapport
Aims 1-2. To develop a Nordic cell therapy program and the next generation NK cell therapy based on selective expansion of adaptive NK cells. We have reported the first clinical result of a Phase I trial with haploidentical NK cells in 16 adult patients with high-risk myeolodysplastic syndrome (MDS) and acute myeloid leukemia (AML) (Björklund et al., Clinical Cancer Research 2018). This trial was developed and performed in collaboration with my team at the Karolinska Institute. Six of the patients achieved complete remission (CR) and five became eligible for and subsequently underwent allogeneic HSCT with three long-term survivors. Some patients achieved molecular remission as determined by sequencing of a set of MDS associated genes. Building on this experience we have designed an improved protocol that involve a culture step with irradiated feeder cells to achieve selective expansion of highly tumor reactive adaptive NK cells. This novel protocol was reported in Liu et al, Cancer Immunology Research 2017. During the past 2 years we have refined the protocol and made the strategic decision to identify superdonors (approximately 1/20) with particularly high numbers of pre-existing adaptive NK cells. Using start material from such donors we get on average 300-fold expansion of self-KIR+ adaptive NK cells in 11 days. With this protocol, one apheresis from a pool of pre-screened superdonors will allow the generation of up to 500 infusions of flat doses of 3x10(9) NK cells in a semi off-the-shelf setting. These pre-clinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing self-recognition. This work represents a Nordic academic initiative and also involves an attempt to harmonize the GMP legislation in US and Europe through a unique transatlantic collaboration. The donor recruitment and collection taking place in Sweden, GMP feeder cell production is performed in Oslo. The clinical trial will be performed in Sweden, Oslo, and Minneapolis (UMN). Status of the adult trial: A) GMP-feeder cell production: The feeder line has been produced and tested in large series of experiments (The results were presented at a selected talk at ASH, San Diego, Dec 2018). Discussions with LMV (Sweden) and SLV (Norway) regarding the extent of testing required to produce a master cell bank have begun and the application is pending Q3 2021. B) Donor recruitment. Ethical permission obtained. 2019-02657. The first 7 donors have undergone apheresis during 2020 and we expect to complete the donor bank during 2021. C) Cell production protocol: The batch protocol has been finalized and the procedure is established at Vecura, Karolinska University Hospital. Tech transfer to the other sites including Oslo is ongoing. D) Clinical trial adult MDS/AML. Application to the NOMA will be sent after three completed validation runs Q4 2021. The protocol has been sent to the FDA and IND filing is expected Q4 2021 at UMN. Aim 3. To establish a platform for off-the-shelf NK cell therapy based on new insights into the early development of NK cells. During the past grant period our team has made significant progress towards the implementation of genetically engineered iPSC-derived off-the-shelf NK cell therapy. We have acquired new technological competences in cell reprogramming, genetic engineering and differentiation. This is partly based on new recruitments in the labs at KI and in Oslo. During 2018-2019 I joined Prof Dan Kaufman´s laboratory at the UCSD for a Sabbatical to learn from their long-standing expertise in iPSC biology. We also partnered with a leading immunotherapy company, Fate Therapeutics, based in San Diego, USA. These new collaborations have so far resulted in one review and two original papers (see list of papers). Cell-based immunotherapy is emerging as a fundamental therapeutic modality in cancer, showing remarkable clinical results in a variety of cancer forms including hematological cancers. However, there are a number of scientific and infrastructural bottlenecks that hinder a wider implementation of cell therapy for cancer. Our efforts in this project and strong international network with academic and industrial partners have led to improved pipelines for developing GMP-compatible cell manipulation protocols in Norway. Through the Scandinavian initiative we are currently address remaining challenges including shipment of off-the-shelf cell therapy products between institutions and hospitals. By process optimisation and generation of centralized production of off-the-shelf cell therapy products we can reduce the costs. This is absolutely critical. For example, effective CAR T cell therapies against B cell malignancies that are approved in the US have not been approved for the same indication in Norway, largely because of the high costs associated with the complicated production of one cellular product per patient. Off-the-shelf therapy with allogeneic NK cells (or T cells for that matter) hold promise to reduce the costs significantly, possibly making this type of therapy available for a larger group of patients. Immunotherapy has become the fourth pillar of cancer treatment, the big brother being immune checkpoint therapy (ICT), which was awarded the Nobel prize in 2018. Alongside the breakthrough of ICT, remarkable results were seen in three different disease settings using autologous T cells transduced with a chimeric antigen receptor (CAR), offering cure to patients with previously incurable disease. The field is still in its infancy and researchers are currently exploring ways to improve CAR-T cell therapy, in terms of efficacy, costs, reproducibility and to be effective in extended groups of patients with different tumor types. Critical to these efforts is the ability to use allogeneic cells as a source for producing clinical products. For T cells this require deletion of the TCR since the transferred T cells will otherwise cause lethal graft versus host disease. NK cells however do not express rearranged receptors and may be ideal candidates for transfer across HLA barriers. In the next decade we will likely see a massive number of clinical trials that will gradually improve our understanding of how to best implement cell therapy in different forms of cancers. It is not unlikely that some of these may be based on off-the-shelf NK cells that are available on demand, much like traditional drugs.

No

2019
Cell-based immunotherapy is emerging as a fundamental therapeutic modality in cancer, showing remarkable clinical results in a variety of cancer forms including hematological cancers. However, there are a number of scientific and infrastructural bottlenecks that hinder a wider implementation of cell therapy for cancer.Our efforts in this project and strong international network with academic and industrial partners have led to improved pipelines for developing GMP-compatible cell manipulation protocols in Norway. Through the Scandinavian initiative we are currently address remaining challenges including shipment of off-the-shelf cell therapy products between institutions and hospitals. By process optimisation and generation of centralized production of off-the-shelf cell therapy products we can reduce the costs. This is absolutely critical. For example, effective CAR T cell therapies against B cell malignancies that are approved in the US have not been approved for the same indication in Norway, largely because of the high costs associated with the complicated production of one cellular product per patient. Off-the-shelf therapy with allogeneic NK cells (or T cells for that matter) hold promise to reduce the costs significantly, possibly making this type of therapy available for a larger group of patients. Our long-term goal is to develop a cell-based immunotherapy program at the international forefront, by translating new insights into the molecular specificity of tumour reactive NK cells into a clinical setting. The experimental work performed in the Lab is supported by a Toppforsk grant from the RCN. With support from HSØ, I currently lead a Scandinavian team-based translational effort to implement new insights in NK cell biology in the clinic. We recently reported the first clinical result of a Phase I trial with haploidentical NK cells in 16 patients with high-risk myeolodysplastic syndrome (MDS) and acute myeloid leukemia (AML) (Clinical Cancer Research 2018). Six of the patients achieved complete remission (CR) and five became eligible for and subsequently underwent allogeneic HSCT with three long-term survivors. NK cell content and cytotoxic potential in the product as well as emergence of donor-derived NK cells in the recipient were all associated with induction of CR. Some patients even achieved molecular remission as determined by sequencing of a set of MDS associated genes. Building on this experience we plan to launch a multi-center cell therapy trial based on an in-house developed method to selectively expand educated NK cells (PI is the main inventor of Patent application WO 2014/037422A1). The outlined effort is a joint Scandinavian initiative to bring a completely new cell therapy product to the clinic. This work is currently supported by the Norwegian Cancer Society and Helse Sør Øst. We will seek further support for the transatlantic trial in a P01 NIH grant with Jeff Miller as a main applicant. The proposed off-the-shelf therapy with a non-engineered and yet highly specific NK cell population represents the first route to clinical testing of missing self-recognition.

The PI (Malmberg) spent 12 months at UCSD, San Diego, USA in the lab of Prof. Dan Kaufman (August 2018 to July 2019). The purpose of the stay was to establish novel technologies to derive iPSC-NK cells for cancer immunotherapy. The collaboration has been very productive, with one printed review article and several manuscripts under preparation including one revised manuscript resubmitted to the Journal of Clinical Investigation. HSØ also support a PhD student, Michelle Sætersmoen who is currently doing a research visit (1 year) in the world leading cancer immunotherapy lab led by Prof Michel Sadelain, who invented the second generation CAR-T cells, at Memorial Sloan Kettering Cancer Institute. Her project concerns a new CAR NK strategy aiming at targeting tumor cell escape by upregulation of HLA-E.

2018
The goal of this project is to develop and implement the next-generation adoptive cancer immunotherapy based on new insights into the differentiation and functional regulation of human NK cells.The present project seeks to address bottlenecks for clinical translation of immunotherapy and promoting the design of innovative Phase I/II trials. The work is based on three specific aims. The launch of a Nordic cell therapy trial based on transfer of metabolically optimized NK cells to patients with very high-risk MDS (aim 1). Establishment of a GMP-compatible pipeline for selective expansion (aim 2) and guided differentiation (aim 3) of highly tumor reactive adaptive NK cells. During 2018 we have made significant progress in all of these aims. Aim 1. To establish a Nordic program for Phase I/II NK cell therapy trials for patients with refractory cancer. Aim 2. To develop the next generation NK cell therapy based on selective expansion of adaptive NK cells. Progress for these two aims goes hand in hand. We have been able to scale-up the protocol for expansion of adaptive NK cells (aim 2) at a level that is beyond our initial expectations. Our GMP-transfer and clinical scale-up of a the research-grade protocol (initially reported in Liu et al, Cancer Immunology Research 2017) allow a 500-fold expansion of self-KIR+ adaptive NK cells in 10 days. With this protocol, one apheresis from a pool of pre-screened superdonors will allow the generation of up to 500 infusions of flat doses of 3x109 NK cells in a semi off-the-shelf setting. These pre-clinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered and yet highly specific NK cell population, representing the first route to clinical testing of missing self-recognition. Another new development in this project is the decision to source superdonors as third part donors for a multi-center trial. By screening over 200 donors we have identified a pool of donors (n=20) that can be used to treat over 1000 patients with highly selected adaptive NK cells. This work represent a true Scandinavian initiative and is a transatlantic collaboration. The donor recruitment and collection taking place in Sweden, GMP feeder cell production is performed in Oslo. The clinical trial will be performed in Oslo, Stockholm, and at University of Minnesota. We are also discussing to run the trial at UCSD, where I am currently doing my Sabbatical. The status of these efforts is as follows: 1) GMP-feeder cell production: The feeder line has been produced and tested in large series of experiments (The results were presented at a selected talk at ASH, San Diego, Dec 2018). Discussions with SLV regarding the extent of testing required to produce a master cell bank have begun and the application is pending Q2 2019. The donor collection. Application to the Swedish LMV will be sent Q2 2019. The study protocol and IMPD are nearly finished and will be discussed with users and thereafter submitted to the regulatory authorities in the respective countries. Expected filing after 3 rounds of large scale-validations is Q4 2019. Aim 3) To establish a platform for off-the-shelf NK cell therapy based on new insights into the early development of NK cells. We have also made significant progress with respect to establishing next generation iPSC-derived NK cells. We have teamed up with Judith Staerk Lab at UiO and have joint post-doc who is performing gene-editing of iPSCs for enhance functionality and persistence in line with the outlined research plan. The basic science underlying these edits was recently published in Nature Communications.
2017
Immunotherapy has rapidly become a cornerstone in the treatment of a large variety of cancer types, and the therapeutic landscape is developing at an unprecedented speed. However, the field is still in its infancy and the potential for translational research in this area to contribute to cancer treatment is higher than ever before.The overarching goal of the planned research is to develop cell-therapy approaches that can increase the fraction of patients that are cured by immunological interventions. During 2017 we have: • Established the robustness of a protocol for ex vivo generation and expansion of adaptive NK cells. Culture of polyclonal NK cells together with HLA-E expressing feeder cells in IL-15 for 14 days lead to an enrichment of adaptive NK cells with distinct KIR specificities, that were determined by the HLA-genotype of the donor. The ex vivo expanded adaptive NK cells gradually obtained a more differentiated phenotype and displayed specific and highly efficient killing of HLA-mismatched paediatric T- and precursor B-cell acute lymphoblastic leukemia (ALL) blasts, previously shown to be resistant to NK cell killing. The cells also showed potent killing of AML and MDS blasts. (Liu et al., Cancer Immunology Research 2017). • We have explored the utility of NK cells as carriers of so called chimeric antigen receptors (CAR), which represent one of the major breakthroughs in cancer immunotherapy during the past years. We have shown that the response of redirected NK-cell subsets against CD19+ targets was dependent on their intrinsic thresholds for activation determined through both differentiation and education by killer cell immunoglobulin-like receptors (KIRs). These findings support the feasibility of primary allogeneic NK cells for CAR engineering and highlight a need to consider NK-cell diversity when optimising efficacy of cancer immunotherapies based on CAR-expressing NK cells. (Oei et al., Cancer Immunology Immunotherapy, 2018, In Press). • We have used several complementary immunological assays to delineate the optimal conditions for NK cell expansion using various feeder cells, beads in combination with cytokines. We have made substantial efforts to show efficacy against a range of primary tumor cells including acute lymphoblastic leukemia and acute myeloid leukemia, which are key targets for initial commercialization of the platform technology. A refined methodological platform allowed us to monitor killing of progenitor cells as well as leukemic stem cells. During the latter part of the project, substantial efforts have been made to identify a suitable industrial partner for licensing of the technology. We are very glad to report a partnership (signed January 2017) with a leading US-based cell therapy company “Fate Therapeutics” that will use our invention for their off-the-shelf NK program. In addition to the licensing of the technology we have entered into a two-year collaborative effort with a significant support for continued effort at Oslo University Hospital (300kUSD/year for 2 years). • The partnership with Fate Therapeutics is a unique opportunity to fast-track the clinical implementation of the invented protocol. We are very excited about the chance to work closely with one of the most influential companies dedicated to develop cell-based cancer immunotherapy. Fate therapeutics begun Phase I/II trials based on their first generation NK cell product during 2017 and we anticipate that our invention will lay the foundation for the next generation NK cell product hitting the clinic end 2018 or shortly thereafter. •. At KI we have published a first clinical trial based on adoptive transfer of NK cells (Björklund at al. Clinical Cancer Research, 2018 In Press.). This trial paves the way for the next Nordic trial to be initiated 2019.
Vitenskapelige artikler
Lachota M, Vincenti M, Winiarska M, Boye K, Zagozdzon R, Malmberg KJ

Prospects for NK Cell Therapy of Sarcoma.

Cancers (Basel) 2020 Dec 11;12(12). Epub 2020 des 11

PMID: 33322371

Tschan-Plessl A, Kalberer CP, Wieboldt R, Stern M, Siegler U, Wodnar-Filipowicz A, Gerull S, Halter J, Heim D, Tichelli A, Tsakiris DA, Malmberg KJ, Passweg JR, Bottos A

Cellular immunotherapy with multiple infusions of in vitro-expanded haploidentical natural killer cells after autologous transplantation for patients with plasma cell myeloma.

Cytotherapy 2021 04;23(4):329-338. Epub 2020 nov 29

PMID: 33268029

Goldenson BH, Zhu H, Wang YM, Heragu N, Bernareggi D, Ruiz-Cisneros A, Bahena A, Ask EH, Hoel HJ, Malmberg KJ, Kaufman DS

Umbilical Cord Blood and iPSC-Derived Natural Killer Cells Demonstrate Key Differences in Cytotoxic Activity and KIR Profiles.

Front Immunol 2020;11():561553. Epub 2020 okt 15

PMID: 33178188

Jacobs B, Schlögl S, Strobl CD, Völkl S, Stoll A, Mougiakakos D, Malmberg KJ, Mackensen A, Aigner M

The Oncometabolite 5'-Deoxy-5'-Methylthioadenosine Blocks Multiple Signaling Pathways of NK Cell Activation.

Front Immunol 2020;11():2128. Epub 2020 okt 6

PMID: 33123121

Patel S, Malmberg KJ

Preventing a shock to the system. Two-pore channel 1 negatively regulates anaphylaxis.

Cell Calcium 2020 Dec;92():102289. Epub 2020 sep 22

PMID: 33027744

Parrot T, Gorin JB, Ponzetta A, Maleki KT, Kammann T, Emgård J, Perez-Potti A, Sekine T, Rivera-Ballesteros O, , Gredmark-Russ S, Rooyackers O, Folkesson E, Eriksson LI, Norrby-Teglund A, Ljunggren HG, Björkström NK, Aleman S, Buggert M, Klingström J, Strålin K, Sandberg JK

MAIT cell activation and dynamics associated with COVID-19 disease severity.

Sci Immunol 2020 09 28;5(51).

PMID: 32989174

Sekine T, Perez-Potti A, Rivera-Ballesteros O, Strålin K, Gorin JB, Olsson A, Llewellyn-Lacey S, Kamal H, Bogdanovic G, Muschiol S, Wullimann DJ, Kammann T, Emgård J, Parrot T, Folkesson E, , Rooyackers O, Eriksson LI, Henter JI, Sönnerborg A, Allander T, Albert J, Nielsen M, Klingström J, Gredmark-Russ S, Björkström NK, Sandberg JK, Price DA, Ljunggren HG, Aleman S, Buggert M

Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.

Cell 2020 10 01;183(1):158-168.e14. Epub 2020 aug 14

PMID: 32979941

Maucourant C, Filipovic I, Ponzetta A, Aleman S, Cornillet M, Hertwig L, Strunz B, Lentini A, Reinius B, Brownlie D, Cuapio A, Ask EH, Hull RM, Haroun-Izquierdo A, Schaffer M, Klingström J, Folkesson E, Buggert M, Sandberg JK, Eriksson LI, Rooyackers O, Ljunggren HG, Malmberg KJ, Michaëlsson J, Marquardt N, Hammer Q, Strålin K, Björkström NK,

Natural killer cell immunotypes related to COVID-19 disease severity.

Sci Immunol 2020 08 21;5(50).

PMID: 32826343

Zhu H, Blum RH, Bernareggi D, Ask EH, Wu Z, Hoel HJ, Meng Z, Wu C, Guan KL, Malmberg KJ, Kaufman DS

Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity.

Cell Stem Cell 2020 Aug 06;27(2):224-237.e6. Epub 2020 jun 11

PMID: 32531207

Pfefferle A, Jacobs B, Haroun-Izquierdo A, Kveberg L, Sohlberg E, Malmberg KJ

Deciphering Natural Killer Cell Homeostasis.

Front Immunol 2020;11():812. Epub 2020 mai 12

PMID: 32477340

Clement D, Goodridge JP, Grimm C, Patel S, Malmberg KJ

TRP Channels as Interior Designers: Remodeling the Endolysosomal Compartment in Natural Killer Cells.

Front Immunol 2020;11():753. Epub 2020 apr 28

PMID: 32411146

Pfefferle A, Jacobs B, Netskar H, Ask EH, Lorenz S, Clancy T, Goodridge JP, Sohlberg E, Malmberg KJ

Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity.

Cell Rep 2019 Nov 19;29(8):2284-2294.e4.

PMID: 31747601

Enqvist M, Jacobs B, Junlén HR, Schaffer M, Melén CM, Friberg D, Wahlin BE, Malmberg KJ

Systemic and Intra-Nodal Activation of NK Cells After Rituximab Monotherapy for Follicular Lymphoma.

Front Immunol 2019;10():2085. Epub 2019 sep 12

PMID: 31572357

Cornillet M, Jansson H, Schaffer M, Hertwig L, Berglin L, Zimmer CL, Johansson H, Ellis E, Isaksson B, Gonzalez-Galarza FF, Middleton D, Malmberg KJ, Sparrelid E, Björkström NK

Imbalance of Genes Encoding Natural Killer Immunoglobulin-Like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer.

Gastroenterology 2019 10;157(4):1067-1080.e9. Epub 2019 jun 21

PMID: 31229495

Goodridge JP, Jacobs B, Saetersmoen ML, Clement D, Hammer Q, Clancy T, Skarpen E, Brech A, Landskron J, Grimm C, Pfefferle A, Meza-Zepeda L, Lorenz S, Wiiger MT, Louch WE, Ask EH, Liu LL, Oei VYS, Kjällquist U, Linnarsson S, Patel S, Taskén K, Stenmark H, Malmberg KJ

Remodeling of secretory lysosomes during education tunes functional potential in NK cells.

Nat Commun 2019 01 31;10(1):514. Epub 2019 jan 31

PMID: 30705279

Jacobs B, Pfefferle A, Clement D, Berg-Larsen A, Saetersmoen ML, Lorenz S, Wiiger MT, Goodridge JP, Malmberg KJ

Induction of the BIM Short Splice Variant Sensitizes Proliferating NK Cells to IL-15 Withdrawal.

J Immunol 2019 02 01;202(3):736-746. Epub 2018 des 21

PMID: 30578306

Saetersmoen ML, Hammer Q, Valamehr B, Kaufman DS, Malmberg KJ

Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells.

Semin Immunopathol 2019 01;41(1):59-68. Epub 2018 okt 25

PMID: 30361801

Oei VYS, Siernicka M, Graczyk-Jarzynka A, Hoel HJ, Yang W, Palacios D, Almåsbak H, Bajor M, Clement D, Brandt L, Önfelt B, Goodridge J, Winiarska M, Zagozdzon R, Olweus J, Kyte JA, Malmberg KJ

Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven by Chimeric Antigen Receptors.

Cancer Immunol Res 2018 04;6(4):467-480. Epub 2018 feb 19

PMID: 29459477

Björklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M, Cooley S, Miller JS, Klimkowska M, Schaffer M, Watz E, Wikström K, Blomberg P, Wahlin BE, Palma M, Hansson L, Ljungman P, Hellström-Lindberg E, Ljunggren HG, Malmberg KJ

Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML.

Clin Cancer Res 2018 Apr 15;24(8):1834-1844. Epub 2018 feb 14

PMID: 29444931

Wagner JA, Rosario M, Romee R, Berrien-Elliott MM, Schneider SE, Leong JW, Sullivan RP, Jewell BA, Becker-Hapak M, Schappe T, Abdel-Latif S, Ireland AR, Jaishankar D, King JA, Vij R, Clement D, Goodridge J, Malmberg KJ, Wong HC, Fehniger TA

CD56bright NK cells exhibit potent antitumor responses following IL-15 priming.

J Clin Invest 2017 Nov 01;127(11):4042-4058. Epub 2017 okt 3

PMID: 28972539

Malmberg KJ, Carlsten M, Björklund A, Sohlberg E, Bryceson YT, Ljunggren HG

Natural killer cell-mediated immunosurveillance of human cancer.

Semin Immunol 2017 Jun;31():20-29. Epub 2017 sep 6

PMID: 28888619

Clancy T, Dannenfelser R, Troyanskaya O, Malmberg KJ, Hovig E, Kristensen V

Bioinformatics Approaches to Profile the Tumor Microenvironment for Immunotherapeutic Discovery.

Curr Pharm Des 2017;23(32):4716-4725.

PMID: 28699527

Malmberg KJ, Sohlberg E, Goodridge JP, Ljunggren HG

Immune selection during tumor checkpoint inhibition therapy paves way for NK-cell "missing self" recognition.

Immunogenetics 2017 08;69(8-9):547-556. Epub 2017 jul 11

PMID: 28699110

Liu LL, Béziat V, Oei VYS, Pfefferle A, Schaffer M, Lehmann S, Hellström-Lindberg E, Söderhäll S, Heyman M, Grandér D, Malmberg KJ

Ex Vivo Expanded Adaptive NK Cells Effectively Kill Primary Acute Lymphoblastic Leukemia Cells.

Cancer Immunol Res 2017 Aug;5(8):654-665. Epub 2017 jun 21

PMID: 28637877

Doktorgrader
Vincent Yi Sheng Oei

Engineering NK Cells Towards Next Generation NK Cell Immunotherapy

Disputert:
september 2018
Hovedveileder:
Karl-Johan Malmberg
Deltagere
  • Artur artur.cieslar-pobuda@ncmm.uio.no Postdoktorstipendiat (annen finansiering)
  • Judith Staerk Forskningsgruppeleder
  • Daniel Alfredo Palacios Or Doktorgradsstipendiat (annen finansiering)
  • Camille Philippon Doktorgradsstipendiat (annen finansiering)
  • Lise Kveberg Forsker (annen finansiering)
  • Dennis Clement Prosjektdeltaker
  • Merete Thune Wiiger Prosjektdeltaker
  • Hanna Julie Hoel Prosjektdeltaker
  • Eivind Heggernes Ask Doktorgradsstipendiat (finansiert av denne bevilgning)
  • Michelle Lu Sætersmoen Prosjektdeltaker
  • Karl-Johan Malmberg Forskningsgruppeleder
  • Jodie Goodridge Prosjektleder

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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