PD-1 antibody "new friend" - MDM2 inhibitor.

TextLi Yuan immunotherapy is able to use the body's immune system to identify, attack and kill tumor cells, but some patients' tumors will have an immune response in the early stages of immunotherapy, but then the tumor will recurother patients will develop false progression, in which the tumor shows growth before eventually shrinkingin addition, 5 to 29 percent of patients will experience hyperprogression, suggesting that immunotherapy actually worsens tumor growth in these patientsJuly 6, a new study published in The Nature sub-journal Cell Death Discovery showed that highly articulative cell lines of MDM2 are more resistant to T-cell-mediated tumors, targeting MDM2 and blocking their expression to enhance the efficacy of immunotherapyimage source: Cell Death Discovery MDM2, known as mouse doubleminute 2 homolog, is an E3 ubiquitin connecting enzymevarious studies have found that when MDM2 amplification occurs or MDM2 proteins are expressed due to poor gene regulation, tumor cells tend to grow faster and are more resistant to immunotherapystudies have shown that MDM2 can help tumors grow and evade the immune system through a variety of mechanisms, for example, MDM2 appears to inactivate the tumor suppressor gene p53 and prevent immune cells from killing tumor cells, and MDM2 is also associated with a higher level of pro-inflammatory protein leukemylonosis 6 (IL-6)in the study, Professor Wafik El-Deiry of Brown University used MDM2 inhibitor AMG-232 to treat the overexpression ovarian cancer cell line of MDM2data show that AMG-232 makes immune cells more effective at killing tumor cells and lowers IL-6 levelsthe combination of AMG-232 and PD-1 antibodies (Pabolizumab) in both T-cell and tumor cell coculture systems resulted in an increase in the lethality of T-cell-mediated tumor cells (below)these results show that immunotherapy can be used in conjunction with MDM2 inhibitors to enhance efficacyPhoto Source: Professor Cell Death Discovery El-Deiry hopes the study will lead to follow-up clinical trials to further assess the safety and effectiveness of the new treatmentBecause MDM2 amplification and overexpression are associated with a variety of cancers, he believes AMG-232 (or similar drugs, including drugs that block MDM2 and related protein MDMX) could be widely used and may even benefit from immunotherapy in patients with normal MDM2 levels"Our findings may provide a good way for patients with over-progressive tumor estimates, "in our study, targeting MDM2 and combining immunotherapy, even if MDM2 did not amplification or overexpression, was effective, using tumor vulnerability to help immunotherapy work better," added Professor El-Deiryaccording to the NextPharma database, in addition to a number of MDM2 inhibitors used in this study, MDM2 inhibitors have entered the clinical development phase, including Unity Biotechnology's UBX0101, University of Michigan/Axan Pharmaceuticals' APG-115, and Novartis's Siremadlinwhether such potential drugs will stand out from the "selection" surrounding PD-1 antibodies, and expect the results of clinical studiesReferences: 1?Ilyas Sahin et al, AMG-232 sensitizes high MDM2-expressing cells to T-cell-mediated killing (Source: Cell Death Discovery) 2 s Drug treatment treatment improve eieness of the betafording for cancer patients (Source: Medical Press)