Genmab — Juli 2018

[gentogen]

Der er fire forskellige:

[gentogen]

CD38 as a novel immune checkpoint and a mechanism of resistance to the blockade of the PD-1/PD-L1 axis.
L Chen, LA Byers, S Ullrich, II Wistuba, XF Qin… - 2017 - ascopubs.org

[gentogen]

Targeting CD38 to improve anti-PD-1/CTLA-4 combination therapy in lung cancer.
L Chen, Y Li, X Yi, DL Gibbons - 2018 - ascopubs.org

[gentogen]

CD38 blockade overcomes the immune resistance to anti-PD-L1 therapy by boosting CD8 T cell response
L Chen, L Diao, Y Yang, X Yi, J Rodriguez, Y Fan… - 2017 - AACR

[gentogen]

CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade
L Chen, L Diao, Y Yang, X Yi, BL Rodriguez, Y Li… - Cancer Discovery, 2018 - AACR

[gentogen]

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."

[gentogen]

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

[Legolas23]

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

[Legolas23]

Hvad tænker du?

[gentogen]

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.

[gentogen]

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.

[gentogen]

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

[gentogen]

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

[gentogen]

jf tidligere link

[gentogen]

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

[Bulder]

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

[Bulder]

... og hvori safety problemet bestod.

[Mcjean]

Hvem siger der var et safety problem Bulder?

[Bulder]

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

[Legolas23]

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.