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Genmab — Juli 2018

Planlagt Fastgjort Låst Flyttet Genmab
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  • G Offline
    G Offline
    gentogen
    wrote on sidst redigeret af
    #954

    Fra nummer to: Conclusions: Targeting CD38 improves the efficacy of anti-PD-1/CTLA-4 combination therapy in lung cancer. CD38 on tumor cells could potentially serve as a novel biomarker of resistance for immune checkpoint inhibition."

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    • 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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