IMTAC Forskning

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Detta centrum har visionen att skapa en virtuell enhet för utveckling av innovativa immunbaserade behandlingsmetoder. Autoimmuna och maligna sjukdomar är de två primära fokus för utveckling av terapeutiska tillämpningar inom ramen för detta tematiska centrum.

Specifika immunologiska metoder som kommer att undersökas för terapeutiska tillämpningar omfattar antikroppar, vacciner och överföring av immunceller (T-celler, NK-celler) som modifierats ex vivo.

Grundläggande forskning ska i första hand inriktas på att belysa nya mekanismer och spridningsvägar och identifiera molekyler och strukturer som skulle kunna användas för behandling. Dessa grundläggande upptäckter kommer att överföras till kunskapsbaserade behandlingsmetoder. Ett urval av dessa terapeutiska möjligheter kommer sedan att testas i kliniska prövningar av säkerhet och effekt.

Petter Höglund

Kort presentation finns på den engelska sidan.

Utvalda publikationer

Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets.
Brodin P, Lakshmikanth T, Kärre K, Höglund P
J. Immunol. 2012 Mar;188(5):2218-26

A modified FCCS procedure applied to Ly49A-MHC class I cis-interaction studies in cell membranes.
Strömqvist J, Johansson S, Xu L, Ohsugi Y, Andersson K, Muto H, et al
Biophys. J. 2011 Sep;101(5):1257-69

Current perspectives of natural killer cell education by MHC class I molecules.
Höglund P, Brodin P
Nat. Rev. Immunol. 2010 Oct;10(10):724-34

NK cell education: not an on-off switch but a tunable rheostat.
Brodin P, Kärre K, Höglund P
Trends Immunol. 2009 Apr;30(4):143-9

The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells.
Brodin P, Lakshmikanth T, Johansson S, Kärre K, Höglund P
Blood 2009 Mar;113(11):2434-41

Rolf Kiessling

Kort presentation finns på den engelska sidan

Utvalda publikationer

[pubmed:21030559]

Antibody-dependent natural killer cell-mediated cytotoxicity engendered by a kinase-inactive human HER2 adenovirus-based vaccination mediates resistance to breast tumors.
Triulzi C, Vertuani S, Curcio C, Antognoli A, Seibt J, Akusjärvi G, et al
Cancer Res. 2010 Oct;70(19):7431-41

Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign.
Poschke I, Mougiakakos D, Hansson J, Masucci G, Kiessling R
Cancer Res. 2010 Jun;70(11):4335-45

Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death.
Mougiakakos D, Johansson C, Kiessling R
Blood 2009 Apr;113(15):3542-5

Frequent loss of HLA-A2 expression in metastasizing ovarian carcinomas associated with genomic haplotype loss and HLA-A2-restricted HER-2/neu-specific immunity.
Norell H, Carlsten M, Ohlum T, Malmberg K, Masucci G, Schedvins K, et al
Cancer Res. 2006 Jun;66(12):6387-94

A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth.
Holmgren L, Ambrosino E, Birot O, Tullus C, Veitonmäki N, Levchenko T, et al
Proc. Natl. Acad. Sci. U.S.A. 2006 Jun;103(24):9208-13

Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor cell lines.
Choudhury A, Charo J, Parapuram S, Hunt R, Hunt D, Seliger B, et al
Int. J. Cancer 2004 Jan;108(1):71-7

Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma.
Nakagomi H, Petersson M, Magnusson I, Juhlin C, Matsuda M, Mellstedt H, et al
Cancer Res. 1993 Dec;53(23):5610-2

Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy.
Kärre K, Ljunggren H, Piontek G, Kiessling R
Nature ;319(6055):675-8

Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts.
Kiessling R, Hochman P, Haller O, Shearer G, Wigzell H, Cudkowicz G
Eur. J. Immunol. 1977 Sep;7(9):655-63

"Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell.
Kiessling R, Klein E, Pross H, Wigzell H
Eur. J. Immunol. 1975 Feb;5(2):117-21

Klas Kärre

Utvalda publikationer

NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo.
Lakshmikanth T, Burke S, Ali T, Kimpfler S, Ursini F, Ruggeri L, et al
J. Clin. Invest. 2009 May;119(5):1251-63

The strength of inhibitory input during education quantitatively tunes the functional responsiveness of individual natural killer cells.
Brodin P, Lakshmikanth T, Johansson S, Kärre K, Höglund P
Blood 2009 Mar;113(11):2434-41

Natural killer cell recognition of missing self.
Kärre K
Nat. Immunol. 2008 May;9(5):477-80

Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants.
van Hall T, Wolpert E, van Veelen P, Laban S, van der Veer M, Roseboom M, et al
Nat. Med. 2006 Apr;12(4):417-24

Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules.
Johansson S, Johansson M, Rosmaraki E, Vahlne G, Mehr R, Salmon-Divon M, et al
J. Exp. Med. 2005 Apr;201(7):1145-55

A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy.
Oliveira A, Thams S, Lidman O, Piehl F, Hökfelt T, Kärre K, et al
Proc. Natl. Acad. Sci. U.S.A. 2004 Dec;101(51):17843-8

LIR-1 expression on lymphocytes, and cytomegalovirus disease in lung-transplant recipients.
Berg L, Riise G, Cosman D, Bergström T, Olofsson S, Kärre K, et al
Lancet 2003 Mar;361(9363):1099-101

A structural basis for LCMV immune evasion: subversion of H-2D(b) and H-2K(b) presentation of gp33 revealed by comparative crystal structure.Analyses.
Achour A, Michaëlsson J, Harris R, Odeberg J, Grufman P, Sandberg J, et al
Immunity 2002 Dec;17(6):757-68

Pivotal role of KARAP/DAP12 adaptor molecule in the natural killer cell-mediated resistance to murine cytomegalovirus infection.
Sjölin H, Tomasello E, Mousavi-Jazi M, Bartolazzi A, Kärre K, Vivier E, et al
J. Exp. Med. 2002 Apr;195(7):825-34

Recruitment and activation of natural killer (NK) cells in vivo determined by the target cell phenotype. An adaptive component of NK cell-mediated responses.
Glas R, Franksson L, Une C, Eloranta M, Ohlén C, Orn A, et al
J. Exp. Med. 2000 Jan;191(1):129-38

Andreas Lundqvist

Kort presentation finns på den engelska sidan

Utvalda publikationer

HER2/HER3 signaling regulates NK cell-mediated cytotoxicity via MHC class I chain-related molecule A and B expression in human breast cancer cell lines.
Okita R, Mougiakakos D, Ando T, Mao Y, Sarhan D, Wennerberg E, et al
J. Immunol. 2012 Mar;188(5):2136-45

Bortezomib Treatment to Potentiate the Anti-tumor Immunity of Ex-vivo Expanded Adoptively Infused Autologous Natural Killer Cells.
Lundqvist A, Berg M, Smith A, Childs R
J Cancer 2011 ;2():383-5

Unlicensed natural born killers.
Lundqvist A, Childs R
Blood 2011 Jun;117(26):6974-5

Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways.
Götherström C, Lundqvist A, Duprez I, Childs R, Berg L, le Blanc K
Cytotherapy 2011 Mar;13(3):269-78

Toxic effects of sorafenib when given early after allogeneic hematopoietic stem cell transplantation.
Yokoyama H, Lundqvist A, Su S, Childs R
Blood 2010 Oct;116(15):2858-9

Major histocompatibility complex-I expression on embryonic stem cell-derived vascular progenitor cells is critical for syngeneic transplant survival.
Ma M, Ding S, Lundqvist A, San H, Fang F, Konoplyannikov M, et al
Stem Cells 2010 Sep;28(9):1465-75

Cutting edge: bortezomib-treated tumors sensitized to NK cell apoptosis paradoxically acquire resistance to antigen-specific T cells.
Lundqvist A, Su S, Rao S, Childs R
J. Immunol. 2010 Feb;184(3):1139-42

Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells.
Berg M, Lundqvist A, McCoy P, Samsel L, Fan Y, Tawab A, et al
Cytotherapy 2009 ;11(3):341-55

Bortezomib treatment and regulatory T-cell depletion enhance the antitumor effects of adoptively infused NK cells.
Lundqvist A, Yokoyama H, Smith A, Berg M, Childs R
Blood 2009 Jun;113(24):6120-7

Primitive quiescent CD34+ cells in chronic myeloid leukemia are targeted by in vitro expanded natural killer cells, which are functionally enhanced by bortezomib.
Yong A, Keyvanfar K, Hensel N, Eniafe R, Savani B, Berg M, et al
Blood 2009 Jan;113(4):875-82

Markus Maeurer

Karl-Johan Malmberg

Kort presentation finns på den engelska sidan

Publikationslista, senaste 8 åren

Jonas Mattsson

Håkan Mellstedt, Anders Österborg, Maria Liljefors

Gruppens övergripande målsättning är att utveckla immunterapi med monoklonala antikroppar, terapeutiska cancervaccin och andra immunstimulerande medel vid hematologiska maligniteter och solida tumörer.

Som en del i denna utveckling ingår också att identifiera och karakterisera nya tumörspecifika målstrukturer. Detta arbete har lett fram till upptäckten av tyrosinkinasreceptorn ROR1 vid kronisk lymfatisk leukemi. I den fortsatta utvecklingen fokuseras forskningen kring karakterisering av ROR1 vid olika tumörsjukdomar samt att utveckla monoklonala antikroppar och små kemiska molekyler, tyrosinkinashämmare, med specificitet för ROR1 för terapeutiskt bruk. Parallellt driver gruppen translationella studier kring behandling med andra antikroppar, ofta i kombination.

Utvalda publikationer

Long-term idiotype vaccination combined with interleukin-12 (IL-12), or IL-12 and granulocyte macrophage colony-stimulating factor, in early-stage multiple myeloma patients.
Hansson L, Abdalla A, Moshfegh A, Choudhury A, Rabbani H, Nilsson B, et al
Clin. Cancer Res. 2007 Mar;13(5):1503-10

Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy.
Daneshmanesh A, Mikaelsson E, Jeddi-Tehrani M, Bayat A, Ghods R, Ostadkarampour M, et al
Int. J. Cancer 2008 Sep;123(5):1190-5

Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells.
Choudhury A, Derkow K, Daneshmanesh A, Mikaelsson E, Kiaii S, Kokhaei P, et al
Br. J. Haematol. 2010 Nov;151(4):327-35

FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment.
Wang B, Kokhaei P, Mellstedt H, Liljefors M
Int. J. Oncol. 2010 Dec;37(6):1599-606

A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease.
Bagnara D, Kaufman M, Calissano C, Marsilio S, Patten P, Simone R, et al
Blood 2011 May;117(20):5463-72

Monoclonal antibodies against ROR1 induce apoptosis of chronic lymphocytic leukemia (CLL) cells.
Daneshmanesh A, Hojjat-Farsangi M, Khan A, Jeddi-Tehrani M, Akhondi M, Bayat A, et al
Leukemia 2012 Jun;26(6):1348-55

Vaccination with dendritic cells loaded with tumor apoptotic bodies (Apo-DC) in patients with chronic lymphocytic leukemia: effects of various adjuvants and definition of immune response criteria.
Palma M, Hansson L, Choudhury A, Näsman-Glaser B, Eriksson I, Adamson L, et al
Cancer Immunol. Immunother. 2012 Jun;61(6):865-79

Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia.
Wierda W, Kipps T, Mayer J, Stilgenbauer S, Williams C, Hellmann A, et al
J. Clin. Oncol. 2010 Apr;28(10):1749-55

Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study.
Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, et al
Ann. Oncol. 2011 Mar;22(3):664-70

Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study.
Wierda W, Padmanabhan S, Chan G, Gupta I, Lisby S, Osterborg A, et al
Blood 2011 Nov;118(19):5126-9

Annika Scheynius

Annika Scheynius forskargrupp

Publikationer av Annika Scheynius (PubMed)

Ola Winqvist

Ola Winqvists forskargrupp

Utvalda publikationer

Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer.
Karlsson M, Marits P, Dahl K, Dagöö T, Enerbäck S, Thörn M, et al
Ann. Surg. Oncol. 2010 Jul;17(7):1747-57

AIRE regulates T-cell-independent B-cell responses through BAFF.
Lindh E, Lind S, Lindmark E, Hässler S, Perheentupa J, Peltonen L, et al
Proc. Natl. Acad. Sci. U.S.A. 2008 Nov;105(47):18466-71

CpG methylation of the IFNG gene as a mechanism to induce immunosuppression [correction of immunosupression] in tumor-infiltrating lymphocytes.
Janson P, Marits P, Thörn M, Ohlsson R, Winqvist O
J. Immunol. 2008 Aug;181(4):2878-86

FOXP3 promoter demethylation reveals the committed Treg population in humans.
Janson P, Winerdal M, Marits P, Thörn M, Ohlsson R, Winqvist O
PLoS ONE 2008 ;3(2):e1612

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma.
Hässler S, Ramsey C, Karlsson M, Larsson D, Herrmann B, Rozell B, et al
Blood 2006 Sep;108(6):1941-8

Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer.
Marits P, Karlsson M, Dahl K, Larsson P, Wanders A, Thörn M, et al
Br. J. Cancer 2006 May;94(10):1478-84

Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator.
Ramsey C, Hässler S, Marits P, Kämpe O, Surh C, Peltonen L, et al
Eur. J. Immunol. 2006 Feb;36(2):305-17

Detection of immune responses against urinary bladder cancer in sentinel lymph nodes.
Marits P, Karlsson M, Sherif A, Garske U, Thörn M, Winqvist O
Eur. Urol. 2006 Jan;49(1):59-70

Eosinophil granulocytes are activated during the remission phase of ulcerative colitis.
Lampinen M, Rönnblom A, Amin K, Kristjansson G, Rorsman F, Sangfelt P, et al
Gut 2005 Dec;54(12):1714-20

Aire deficient mice develop multiple features of APECED phenotype and show altered immune response.
Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kämpe O, et al
Hum. Mol. Genet. 2002 Feb;11(4):397-409

ImmunologiImmunterapi