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

Immunotherapy can use the body's immune system to identify, attack, and kill tumor cells, but some patients' tumors respond to immunity in the early stages of immunotherapy, but then the tumor returns.
other patients will experience false progression, in which the tumor shows growth before eventually shrinking.
addition, 5 to 29 percent of patients show hyperprogression, suggesting that immunotherapy actually worsens tumor growth in these patients.
A new study published July 6 in the journal Cell Death Discovery, a sub-journal of Nature, shows that MDM2's highly expressed cell line is more resistant to T-cell-mediated tumor damage, targeting MDM2 and blocking its expression can enhance the effectiveness of immunotherapy.
photo source: Cell Death Discovery MDM2, known as mouse doubleminute 2 homolog, is an E3 ubiganic connective enzyme.
studies have found that tumor cells tend to grow faster and become more resistant to immunotherapy when MDM2 amplification occurs or MDM2 proteins are over-expressed due to improper gene regulation.
that MDM2 can help tumors grow and evade the immune system through a variety of mechanisms.
, for example, MDM2 appears to cause the tumor suppressor gene p53 to insulcen and prevent immune cells from killing tumor cells, and MDM2 is also associated with higher levels of the inflammatory protein albumin 6 (IL-6).
study, Professor Wafik El-Deiry of Brown University treated MDM2's overexpressed ovarian cancer cell line with MDM2 inhibitor AMG-232.
data show that AMG-232 makes immune cells kill tumor cells more effectively and lowers IL-6 levels.
The combined use of AMG-232 and PD-1 antibodies (Paboli pearl monoantigen) in both T-cells and tumor cell co-culture systems has enhanced the lethality of tumor cells mediated by T-cells (see figure below).
results suggest that immunotherapy can be used in combination with MDM2 inhibitors to enhance efficacy.
: 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 treatment.
Because the amplification and overexpression of MDM2 are associated with a variety of cancers, he believes that AMG-232 (or similar drugs, including drugs that block MDM2 and related protein MDMX) may be widely used and may even benefit patients with normal MDM2 levels of tumors from immunotherapy.
"For patients with tumors who are predicting over-progress, our results may present a good approach," he said.
In our study, even if MDM2 did not amplification or overexpression, targeting MDM2 in combination with immunotherapy had good results, and this combination could take advantage of tumor vulnerability to help immunotherapy work better.
," Adds Professor El-Deiry.
in addition to the AMG-232 (Phase II Clinical) used in this study, a number of MDM2 inhibitors from around the world are in clinical development, including Unity Bioy's UBX0101, University of Michigan/AXA Pharmaceuticals' APG-115, and Novartis' Siremadlin, according to the NextPharma database.
whether these potential drugs can stand out from the "selection" surrounding PD-1 antibodies and look forward to the results of clinical studies.
: 1 s Ilyas Sahin et al, AMG-232 sensitizes high MDM2-expressing cells to T-cell-mediated killing (Source: Death Cell Discovery) 2 s Drug treatment treatment effects of immunotherapy for patients (Source: Medical Press)