<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1"^^ . "Point mutations in the isocitrate dehydrogenase (IDH) genes\r\nare\r\nan\r\nearly,\r\nif\r\nnot\r\nthe\r\nearliest\r\nevent\r\nduring\r\nthe\r\ndevelopment\r\nof\r\ngliomas\r\nand\r\nother\r\ntumors,\r\nsuch\r\nas\r\nacute\r\nmyeloid\r\nleukemia\r\n(AML).\r\nAmong\r\ngrade\r\nII\r\nand\r\ngrade\r\nIII\r\ngliomas,\r\nmore\r\nthan\r\n80\r\n%\r\ncarry\r\nan\r\nIDH\r\nmutation.\r\nIn\r\nthese\r\nentities,\r\nmutations\r\nalmost\r\nexclusively\r\naffect\r\nthe\r\ncatalytically\r\ncritical\r\narginine\r\nresidue\r\nof\r\nthe\r\ncytoplasmic\r\nIDH1,\r\nleading\r\nto\r\nthe\r\namino\r\nacid\r\nexchange\r\nto\r\nhistidine\r\n(R132H).\r\nThis\r\nand\r\nother\r\nIDH\r\nmutations\r\nresult\r\nin\r\na\r\nneomorphic\r\nenzyme\r\nfunction\r\nand\r\nthe\r\nproduction\r\nof\r\nthe\r\noncometabolite\r\n2-­‐hydroxyglutarate\r\n(2-­‐HG)\r\nand\r\nthus\r\ngenome-­‐wide\r\nhypermethylation\r\nand\r\nmalignant\r\ntransformation.\r\nThe\r\nwork\r\nat\r\nhand\r\ndemonstrates\r\nthe\r\nsuitability\r\nof\r\nIDH1R132H\r\nas\r\na\r\ntarget\r\nfor\r\nimmunotherapy\r\nin\r\nan\r\nMHC-­‐humanized\r\nmouse\r\nmodel,\r\nA2.DR1.\r\nPeptides\r\nencompassing\r\nthe\r\nmutated\r\nregion\r\nbound\r\nMHC\r\nclass\r\nII\r\nin\r\nvitro\r\nand\r\ninduced\r\na\r\nmutation-­‐specific\r\nCD4+\r\nT\r\nhelper\r\n(Th)\r\nresponse\r\nin\r\nvivo,\r\nwhose\r\nantigen-­‐specificity\r\npersisted\r\nin\r\na\r\nspecific\r\nT\r\ncell\r\nline\r\nand\r\nclone\r\nand\r\nwhich\r\nwas\r\naccompanied\r\nby\r\nIDH1R132H-­‐specific\r\nantibody\r\nproduction.\r\nTo\r\ndetect\r\nIDH1R132H-­‐specific\r\nIgG\r\nin\r\nmouse\r\nand\r\nhuman\r\nserum,\r\na\r\npeptide-­‐coated\r\nELISA\r\nwas\r\nestablished.\r\nSeveral\r\ntested\r\npatients\r\nwith\r\nIDH1R132H+\r\ngliomas\r\nshowed\r\nspontaneous\r\nIDH1R132H-­‐specific\r\nantibody\r\nand\r\nCD4+\r\nTh1\r\ncell\r\nresponses.\r\nPreventive\r\nand\r\ntherapeutic\r\nIDH1R132H\r\npeptide\r\nvaccination\r\nof\r\nA2.DR1\r\nmice\r\nbearing\r\nsyngeneic\r\nIDH1R132H+\r\nsarcomas\r\nresulted\r\nin\r\nan\r\neffective\r\nmutation-­‐specific\r\nantitumor\r\nimmune\r\nresponse\r\ncapable\r\nof\r\ncontrolling\r\ntumor\r\ngrowth\r\nin\r\na\r\nCD4+\r\nT\r\nand\r\nB\r\ncell-­‐\r\ndependent\r\nmanner.\r\nFunctionality\r\nof\r\nthe\r\nvaccine\r\nwas\r\nevidenced\r\nby\r\nloss\r\nof\r\nIDH1R132H\r\nexpression\r\nin\r\nIDH1-­‐transduced\r\nsarcomas\r\nand\r\ninfiltration\r\nof\r\nIDH1R132H-­‐specific\r\nCD4+\r\nT\r\ncells\r\ninto\r\nthe\r\ntumor\r\nbulk.\r\nCompared\r\nto\r\ntherapeutic\r\nMHC\r\nII-­‐mediated\r\npeptide\r\nvaccination\r\nagainst\r\nthe\r\nwell-­‐established\r\ncancer\r\ntestis\r\nantigen\r\n1\r\n(CTAG1B,\r\nNY-­‐ESO-­‐1),\r\nIDH1R132H\r\nis\r\na\r\nrelevant\r\nneoantigen\r\nof\r\ncomparable\r\nefficacy.\r\nGiven\r\nthe\r\nIDH1R132H-­‐mediated\r\naccumulation\r\nof\r\n2-­‐HG,\r\nthe\r\neffect\r\nof\r\nthis\r\nmetabolite\r\non\r\nhuman\r\nT\r\ncells\r\nis\r\nof\r\npotential\r\nrelevance\r\nduring\r\nIDH1R132H-­‐targeted\r\nimmunotherapy.\r\nHowever,\r\nneither\r\nhuman\r\nperipheral\r\nCD4+\r\nnor\r\nCD8+\r\nT\r\ncell\r\nfunctions\r\nfrom\r\nhealthy\r\nsubjects\r\nwere\r\naffected\r\nby\r\n2-­‐HG.\r\nIn\r\nconclusion,\r\nIDH1R132H\r\nrepresents\r\na\r\npotentially\r\nclinically\r\nmeaningful\r\ntumor-­‐specific\r\nneoantigen.\r\nConceptually,\r\npatients\r\nwith\r\nlow-­‐grade\r\nand\r\nanaplastic\r\ngliomas\r\nwith\r\na\r\nhigh\r\nII\r\nprevalence\r\nof\r\nthe\r\nIDH1R132H\r\nmutation\r\nrepresent\r\na\r\npatient\r\npopulation,\r\nwhich\r\nmay\r\nparticularly\r\nbenefit\r\nfrom\r\na\r\ntumor\r\nvaccine,\r\nas\r\nthere\r\nis\r\ncurrently\r\nno\r\ntherapy\r\npreventing\r\nrecurrence\r\nin\r\nthis\r\nrelatively\r\nyoung\r\nand\r\nimmunologically\r\ncompetent\r\npatient\r\npopulation.\r\nMoreover,\r\npatient\r\ngroups\r\nwith\r\nother\r\nIDH1R132H-­‐mutated\r\ntumors\r\nmight\r\npotentially\r\nalso\r\nbenefit\r\nfrom\r\nsuch\r\na vaccine."^^ . "2014" . . . . . . . "Theresa"^^ . "Schumacher"^^ . "Theresa Schumacher"^^ . . . . . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1 (PDF)"^^ . . . "Dissertation Schumacher Theresa.pdf"^^ . . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1 (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1 (Other)"^^ . . . . . . "preview.jpg"^^ . . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1 (Other)"^^ . . . . . . "medium.jpg"^^ . . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1 (Other)"^^ . . . . . . "small.jpg"^^ . . . "A cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1 (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #16805 \n\nA cancer immunotherapy approach targeting mutant isocitrate dehydrogenase 1\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .