Can res: combined with CK2 inhibitor and immunocheckpoint inhibitor to eliminate multiple tumors

September 6, 2018 / bioun / - according to a recent study published in cancer research by the Westar Institute in Philadelphia, US, a new type of casein kinase 2 (CK2) inhibitor and an immunocheckpoint inhibitor can significantly enhance the anti-cancer effect of the two inhibitors Cancer research immunosuppressant has been approved for several cancers, including some lung and colon cancers, but not all patients receiving this immunotherapy can benefit from it More in-depth understanding of why some patients have no response to immunosuppressive checkpoint inhibitors can find new targets for combination therapy to improve clinical efficacy "An immune cell called myeloid derived suppressor cell (MDSC) is thought to be associated with tumor tolerance to a variety of therapies, including immunocheckpoint therapy." Said Dr Dmitry I gabrilovich, research leader, leader of the immunology, microenvironment and transfer project team at Westad and Professor Christopher M Davis "Our previous studies have found that the enrichment of the most abundant MDSC, polymorphonuclear MDSC (pmn-mdsc), is mainly due to the down regulation of Notch signal, partly due to the activity of CK2." Based on these findings, Dr gabrilovich and his colleagues began to find out whether they could be combined with CK2 inhibitors and immunocheckpoint inhibitors to enhance their antitumor effects "Our new results suggest that using a CK2 inhibitor to manipulate the tumor microenvironment may make patients more sensitive to immunosuppressive checkpoint inhibitors and thus improve their clinical efficacy, although we need to confirm it in clinical trials." Ayumi Hashimoto, a postdoctoral researcher in Dr gabrilovich's group and the first author of the study, said The researchers found that the combination of CK2 inhibitor bms-595 and anti-ctla-4-mlgg2a had a good therapeutic effect in three different mouse tumor models (lung cancer, rectal cancer and lymphoid cancer) More than 60% of the mice in the combined treatment group completely cleared the tumor, while none of the mice in the single treatment group cleared the tumor The researchers analyzed the mechanism of bms-595 and found that pmn-mdsc and tumor associated macrophages (TAM) are the two main target cells in the tumor microenvironment affected by CK2 The number of pmn-mdscs in tumors did not decrease, but the number of pmn-mdscs in spleen decreased, while TAMs in tumors decreased "Our results show that CK2 inhibitors inhibit the differentiation of pmn-mdscs and TAMs, which means that it can prevent the precursor cells of these cells from producing these cells This leads to a decrease in immunosuppressive pmn-mdscs and tumor promoting TAMs, thus enhancing the efficacy of immunosuppressive checkpoint inhibitors " Gabrielovich added Reference: Ayumi Hashimoto et al, initiation of case in kinase 2 interrupts differentiation of myoid cells in cancer and enhancements the efficiency of immunity in mice, cancer research (2018) Doi: 10.1158/0008-5472.can-18-1229