Good News for Target Therapy Treatment: CMU President Mien-Chie Hung’s International Research Team Published Research Findings on Cancer Cell Journal
Date：July 19, 2019
The mystery of why PD-L1 cannot be detected in cancer patients' clinical specimen has been solved! China Medical University (CMU) President Mien-Chie Hung led an international research team that adopted a new strategy by using specific enzymes to remove the glycosylation of PD-L1 on cells, so that PD-L1 protein will not be blocked by glycan structure and therefore be identified by PD-L1 antibodies. In other words, the cancer target therapy in clinical medicine has become more precise and can be widely used in treating various cancer groups to benefit more immunotherapy patients.
The study “Removal of N-linked glycosylation enhances PD-L1 detection and predicts anti-PD-1/PD-L1 therapeutic efficacy” was published on the journal Cancer Cell on July 19th, 2019. It received high attention and praises from the international medical community.
President Hung, who aims to “terminate cancer”, said that in the current target therapy for cancers, anti-PD-L1/PD-1 immunotherapy has become a revolutionary principle. It brings significant therapeutic effect to 20-40% of patients in average. However, a previous unsolved phenomenon has long existed in clinical trials and research. Theoretically, only PD-L1-positive patients are responsive to “anti-PD-L1/PD-1” treatment. However, clinically, there are 10-20% PD-L1-negative patients remained responsive to anti-PD-L1/PD-1 treatment. This has been a clinical mystery for a long time.
“We have solved this mystery.” said President Hung happily. It turns out the current methods for detecting PD-L1 are not perfect, and the expression levels of PD-L1 in patients' specimen is not an ideal biomarker to effectively determine whether patients are suitable for the accurate anti-PD-L1/PD-1 immunotherapy.
It is well known that PD-L1 is a highly glycosylated protein. The research team therefore hypothesize that in the patient tissue samples of a particular group, there may be a specific glycan structure that that are coated with PD-L1 proteins on the outside, thus hindering the binding of anti-PD-L1 antibodies (mAb clone 28-8) in clinical detection of PD-L1 and resulting in false negative outcomes. Therefore, this particular group of patients’ cancer tissue specimen do have PD-L1 expressions and respond positively to anti-PD-1/PD-L1 treatment. Unfortunately, they lost the chance to receive this immunotherapy due to false negative detection result.
President Hung’s research group has thus developed a new therapeutic strategy, which is to apply specific enzymes to remove the glycosylation on the PD-L1 protein, so that it can be recognized by the PD-L1 antibody.
In tissue microarrays and patient samples, President Hung’s team proved this new strategy effective in detecting approximately 16% of the total patient population. These patients were PD-L1-positive and shown positive results in anti-PD-1/PD-L1 treatment, while with traditional method they were diagnosed with PD-L1-negative.
This newly developed testing strategy for cancer immunotherapy can identify PD-L1-positive patients more accurately and further make them benefit from the immunotherapy. Most of all, this new strategy may be widely used in various types of cancer, which brings great clinical values.