Genmab — Juli 2018
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Ser ud til at ADC terapierne er lidt i unåde. https://www.fiercebiotech.com/biotech/patient-death-prompts-fda-hold-mersana-s-lead-cancer-adc?mkt_tok=eyJpIjoiWldRM05qUTVaVFk0WW1FMyIsInQiOiJoWXJOZTBhNzhjNWdlXC9sU3FWeTJVNFwvbVUyalc4YVpDWm1JS2FleFhXZlJWcVY2Tk5TN3VaeFo3ek9HOHFyQVIydjZ3RlM3U09JTWY4NDdsVDlFdlhNUjhJQmJvQ01TaTRmdElCYWdEUkwyUk1Fc1lsaXdMWlFPSklhK25xVUVQIn0%3D&mrkid=41140432
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Limo Chen, CD38-mediated immunosuppression as a mechanism of tumor cell
escape from PD-1/PD-L1 blockade http://cancerdiscovery.aacrjournals.org/content/candisc/early/2018/07/14/2159-8290.CD-17-1033.full.pdf -
The mechanism of immune resistance to anti-PD- L1/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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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 -
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 -
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. -
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. -
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 -
Kildeangivelse: Downloaded from cancerdiscovery.aacrjournals.org on July 21, 2018.
2018 American Association for Cancer Research
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