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Genmab — Juli 2018

Planlagt Fastgjort Låst Flyttet Genmab
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Denne tråd er blevet slettet. Kun brugere med emne behandlings privilegier kan se den.
  • G Offline
    G Offline
    gentogen
    wrote on sidst redigeret af
    #955

    tumor bearing mice treated with combined PD-1 and CTLA-4 blocking antibodies developed resistance through the up-regulation of CD38, and that targeting CD38 abolished the resistance in a manner dependent on B7-costimulation

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    • Legolas23L Offline
      Legolas23L Offline
      Legolas23
      wrote on sidst redigeret af
      #956

      Bliver spændende om BMS-studierne kommer op med resultater, som underbygger.

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      • Legolas23L Offline
        Legolas23L Offline
        Legolas23
        wrote on sidst redigeret af
        #957

        Hvad tænker du?

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        • G Offline
          G Offline
          gentogen
          wrote on sidst redigeret af
          #958

          Fra nummer fire hedder det: "Overall the therapeutic studies demonstrate that combination CD38 and PD-L1 blockade substantially reduces primary tumor burden and
          metastases, that CD38 can be used in combination or in a sequential manner upon the
          acquisition of resistance, and that targeting CD38 or the downstream adenosine
          signaling is highly effective.

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          • G Offline
            G Offline
            gentogen
            wrote on sidst redigeret af
            #959

            To model how CD38-blocking strategies might be translated into the clinic for patients
            with disease refractory to anti-PD-1/PD-L1, we tested sequential treatment after the
            development of resistance to anti-PD-L1 by treating animals with anti-CD38 antibody
            alone.

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            • G Offline
              G Offline
              gentogen
              wrote on sidst redigeret af
              #960

              We observed a substantial inhibition of tumor growth with an associated
              enhancement of the effector CD8+
              and CD4+
              T cell responses and blunting of the
              suppressor CD4+
              T regulatory and MDSC populations, highlighting that CD38 is an
              independent factor in treatment-induced resistance

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              • G Offline
                G Offline
                gentogen
                wrote on sidst redigeret af
                #961

                Kildeangivelse: Downloaded from cancerdiscovery.aacrjournals.org on July 21, 2018. © 2018 American Association for Cancer Research

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                • G Offline
                  G Offline
                  gentogen
                  wrote on sidst redigeret af
                  #962

                  jf tidligere link

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                  • G Offline
                    G Offline
                    gentogen
                    wrote on sidst redigeret af
                    #963

                    Jeg er ikke ekspert nok til at tænke så meget, men det lyder meget overbevisende....så jeg bliver bestemt ikke overrasket, hvis studier fortsætter

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                    • BulderB Offline
                      BulderB Offline
                      Bulder
                      wrote on sidst redigeret af
                      #964

                      Men det forklarer stadig ikke hvorfor kontrolgruppen i dara-atezo s
                      tudiet klarede sig lige så godt som eksp. gruppen

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                      • BulderB Offline
                        BulderB Offline
                        Bulder
                        wrote on sidst redigeret af
                        #965

                        ... og hvori safety problemet bestod.

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                        • M Offline
                          M Offline
                          Mcjean
                          wrote on sidst redigeret af
                          #966

                          Hvem siger der var et safety problem Bulder? 😉

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                          • BulderB Offline
                            BulderB Offline
                            Bulder
                            wrote on sidst redigeret af
                            #967

                            In addition to the lack of benefit, the DMC noted a numerical increase in mortality-related events in the combination arm.

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                            • Legolas23L Offline
                              Legolas23L Offline
                              Legolas23
                              wrote on sidst redigeret af
                              #968

                              Ja, man frøs/stoppede pga for mange dødsfald, også ville man undersøge grunden bag. Et dicideret stop har jeg ikke hørt. Andre forsøg med tecentric er også stoppet, så der sker noget i kombien,man lige skal have styr på.

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                              • G Offline
                                G Offline
                                gentogen
                                wrote on sidst redigeret af
                                #969

                                Jeg er med på safetyproblemet, men konklusionen er stadigvæk, at "The mechanism of immune resistance to anti-PDL1/PD-1
                                therapy caused by CD38 provides an evident rationale for recruitment of
                                cancer patients for clinical trials of anti-CD38 in combination with anti-PD-L1/PD-1 to
                                prevent therapy resistance and further enhance anti-tumor efficacy."

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                                • G Offline
                                  G Offline
                                  gentogen
                                  wrote on sidst redigeret af
                                  #970

                                  De finder også, at "CD38-mediated
                                  resistance could occur in a broad variety of cancer types"

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                                  • SolsenS Offline
                                    SolsenS Offline
                                    Solsen
                                    wrote on sidst redigeret af
                                    #971

                                    Der foreligge jo en teori om, at det er et trdie stof der skaber problemerne og at det er protokollen, der fejlede. Lad os se om ikke vi snart kunne se noget fra nivolumab forsøgene.

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                                    • G Offline
                                      G Offline
                                      gentogen
                                      wrote on sidst redigeret af
                                      #972

                                      The emerging
                                      evidence suggests a multi-faceted immunosuppressive role for CD38 in regulating
                                      tumor immune microenvironment.

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                                      • G Offline
                                        G Offline
                                        gentogen
                                        wrote on sidst redigeret af
                                        #973

                                        Men som de siger "many questions about how
                                        best to incorporate CD38 into immunotherapy strategies will need to be studied in
                                        prospective clinical trials of CD38 blockade!

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                                        • G Offline
                                          G Offline
                                          gentogen
                                          wrote on sidst redigeret af
                                          #974

                                          Nu er jeg alt andet end ekspert, meh hæfede mig lidt ved sætningen fra tidligere citat, at "CD38 can be used in combination or in a sequential manner". Det sidste blev vel ikke afprøvet i det afbrudte studie

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