Presentation on theme: "Jakub Golab Department of Immunology Medical University of Warsaw"— Presentation transcript:
1 Jakub Golab Department of Immunology Medical University of Warsaw Therapeutic applications of anti-CD20 monoclonal antibodies - tumors and beyondCHMP/PDCO/CMDh Presidency meetingJakub GolabDepartment of ImmunologyMedical University of Warsaw
2 Nobel prize in 1901 Emil Adolf von Behring Marburg University "for his work onserum therapy…”
5 Nobel prize in 1984 "for the discovery of the principle for production Georges KöhlerBasel Institute for ImmunologyCésar MilsteinMRC Laboratory of Molecular BiologyCambridge"for the discovery ofthe principle for productionof monoclonal antibodies"
6 Types of monoclonal antibodies murine Fabmurine FVFcFabmurine antibodychimeric antibody(66% of human sequence)humanised antibody(90% of human sequence)human antibody(100% of human sequence)
12 Anti-CD20 monoclonal antibodies AntibodyClinical statusCharacteristicsOriginIsotypeRituximabapprovedchimericIgG1Tositumomab*murineIgG2aOfatumumabhumanIbritumomab**Ocrelizumabphase 3humanizedVeltuzumabphase 2ObinutuzumabPRO131921AME-133LFB-R603/EMAB-6phase 1* radioimmunoconjugate bound to 131iodine** radioimmunoconjugate bound to 90ytrium
13 Development of novel anti-CD20 monoclonal antibodies:
14 Rituximab-mediated complement dependent cytotoxicity against control and statin-treated lymphoma cellsWiniarska et al. PLoS Med. 2008;5(3):e64.
15 and why this finding might be important … ? Because million people all over the world are long-term statin usersThe estimated number of people that should be using statins at the time being is 200 million
16 Number of cellsFluorescence intensityWiniarska et al. PLoS Med. 2008;5(3):e64.
17 PE – intracellular tail of CD20 FITC – extracellular loop of CD20 Winiarska et al. PLoS Med. 2008;5(3):e64.
21 Cancer patients are unlikely to give up these treatments!!! Cancer is a disease of elderly peopleIncreasing age is associated with:complex changes in physiology (alterations in renal and hepatic functions, decreased bone marrow reserve)Increased number of comorbid diseases (cardiovascular diseases, diabetes, rheumatic diseases, neuropsychiatric disorders)Cancer patients are unlikely togive up these treatments!!!Elderly people usually take multiple different drugs:antidiabeticsstatinsdiureticsβ-blockersantidepressantsanti-inflammatory drugs
23 Potential future uses of anti-CD20 monoclonal antibodies rheumatoid arthritismultiple sclerosissystemic lupus erythematosusautoimmune anemiaautoimmune hemolytic anemiapure red cell aplasiaidiopathic thrombocytopenic purpura (ITP)Wegener's granulomatosisbullous skin disorders (pemphigus, pemphigoid)type 1 diabetes mellitusSjogren's syndromethyroid-associated ophthalmopathyA new study from Norway suggests that rituximab (together with methotrexate) might help patients with chronic fatigue syndrome. A clinical trial is ongoing.
24 AcknowledgementsMagdalena Winiarska, Jacek Bil, Dominika Nowis, Małgorzata Wańczyk, Marcin Makowski, Tomasz Świtaj, Kamil Bojarczuk, Eliza Głodkowska, Piotr Mrówka, Paweł Salwa, Tadeusz Issat, Zuzanna Kurzaj, Witold Lasek, Tomasz Stokłosa, Marek JakóbisiakDepartment of ImmunologyMedical University of WarsawCezary WójcikDepartment of Anatomy and Cell Biology, IUSM, USAGrzegorz M . WilczyńskiNencki Institute of Experimental BiologyWendy J.M. MackusPatrick J. EngelbertsPaul W.H.I. ParrenGenmab, Utrecht, The NetherlandsŁukasz BojarskiInternational Institute of Molecular and Cell Biology, WarsawMaciej Siński, Ewa Wilczek, Grzegorz Basak, Zbigniew Gaciong, Elżbieta Górska, Maria WąsikAnna Dąbrowska-IwanickaMaria Sklodowska-Curie Memorial Cancer CenterKrzysztof WarzochaInstitute of Hematology, WarsawKazimierz SułekDepartment of Clinical Hematology, Military Medical InstituteSome figures were prepared using Servier Medical Art (www.servier.com)
25 T E A M Improvement of antitumor effectiveness of photodynamic therapy In coooperation with:Patrizia Agostinis (Catholic University of Leuven, Belgium)Michael Hamblin (Wellmans Center of Photomedicine, Boston, USA)Jacek Capala (National Institutes of Health, Bethesda, USA)TEAM members:Dr. Małgorzata FirczukDr. Magdalena WiniarskaMSc. Małgorzata JodłowskaMSc. Angelika SzokalskaBSc. Justyna ChlebowskaBSc. Paweł SalwaBSc. Kamil BojarczukBSc. Magdalena GabrysiakTEAM coordinator:prof. Jakub GolabTEAM consultant:Dr. Dominika Nowis
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