EMBO Mol Med: Revealing why the use of DR5 agonist antibodies to treat solid tumors such as triple-negative breast cancer and ovarian cancer has repeatedly failed

News from April 20, 2021/bioon.
com" target="_blank">/---The lack of effective immune cell infiltration is an important obstacle to the immunotherapy of solid tumors.
Activating the death receptor-5 (DR5) antibody enriched in solid tumors to achieve tumor cell reduction through external apoptotic cytotoxicity is still an important alternative treatment strategy and a promising treatment for solid tumors Strategy.
In the past few decades, many DR5 agonist antibodies entered clinical trials after successfully controlling tumors in immunodeficiency tumor xenografts.
However, all clinically tested DR5 agonist antibodies proved to be unsuccessful in phase II bioon.
com/course_video/lin-chuang-shi-yan-de-feng-xian-jian-kong239833.
html">clinical trials of solid tumors and failed to significantly improve survival rates.
This has prompted efforts to develop second-generation DR5 agonists in order to achieve super large-scale apoptotic cytotoxicity in tumors.
As the control of the immune system has become a powerful tool for tumor treatment, before realizing the true clinical potential of DR5 agonist antibodies, there is still a major question: whether there is an undiscovered immune evasion mechanism that offsets the anti- bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor activity and may lead to DR5 What about the clinical failure of agonist antibodies?

bioon.
com" target="_blank">bioon.
com/course_video/lin-chuang-shi-yan-de-feng-xian-jian-kong239833.
html">Clinical trial bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor

In view of the elevated levels of PD-L1 carried by triple-negative bioon.
com/tags/%E4%B9%B3%E8%85%BA%E7%99%8C/">breast cancer (TNBC), ovarian cancer and other solid tumors, and considering the lack of immune activation function in the combination therapy of albumin-bound paclitaxel (nab-paclitaxel) and DR5 agonist, from In a new study, researchers from research institutions such as the University of Virginia in the United States tested a view that PD-L1-mediated immune evasion could potentially lead to lower anti-tumor responses of DR5 agonist antibodies.
To this end, they used a variety of clinical DR5 agonist antibodies, a variety of solid tumor cell lines, and animal bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor models with sufficient immunity .
Related research results were recently published in the journal EMBO Molecular Medicine, with the title of the paper "Unexpected PD-L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies".

bioon.
com/tags/%E4%B9%B3%E8%85%BA%E7%99%8C/">Breast cancer bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumors

png" target="_blank">

png" target="_blank">

These authors found that in the solid tumor cell lines tested, a variety of clinical DR5 agonist antibodies stabilized PD-L1 in tumor cell lysates.

Blocking the death-inducing signal complex (DISC) containing caspase-8 can inhibit the stabilization of PD-L1.
Compared with animals treated with control IgG1, bioon.

bioon.

bioon.

bioon.

bioon.

bioon.

png" target="_blank">

bioon.

bioon.

bioon.

bioon.

Reference materials: Tanmoy Mondal et al.
Unexpected PD-L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies .
EMBO Molecular Medicine, 2021, doi:10.
15252/emmm.
202012716.
Unexpected PD-L1 immune evasion mechanism in TNBC, ovarian, and other solid tumors by DR5 agonist antibodies