Chen, Jia-Shiong published the artcileCC-01 (chidamide plus celecoxib) modifies the tumor immune microenvironment and reduces tumor progression combined with immune checkpoint inhibitor, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Scientific Reports (2022), 12(1), 1100, database is CAplus and MEDLINE.
Immune checkpoint inhibitors (ICIs) have shown clin. benefit in solid tumors, with modest rates of clin. response. Hence, improved therapeutic approaches need to be investigated. Herein, we assessed a combination of chidamide plus celecoxib (called CC-01) combined with programmed cell death protein 1 (PD-1) blockade in a CT26 model as potent tumor microenvironment (TME) regulator. The antitumor activity was assessed by measuring tumor size, overall response rate, and survival rate. Immune profiling of tumor-infiltrating lymphocytes was performed by flow cytometry. Tumor tissues were assessed by chip assay to predict the possible pathway. Tumor size was significantly reduced in mice treated with CC-01 combined with or without anti-PD-1 antibody, however the triple combination therapy consistently demonstrated that it significantly increased both the ORR and survival rate in term of clin. applications. In the combination group, immune landscape profiling revealed decreased populations of immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Anal. of the mouse tumor chip data using Gene Ontol. enrichment anal. of biol. processes revealed that the triple combination upregulated genes associated with responses to interferon-gamma. Our results demonstrated that CC-01 possessed potent TME regulatory properties, augmenting the antitumor effect when combined with ICIs. This antitumor effect was achieved by altering the immune landscape in TILs (tumor-infiltrating lymphocytes) and was associated with immune cell activation in the TME. Furthermore, CC-01 demonstrated potent anticancer immune response activity, mainly reducing the number and function of several immunosuppressive cells. The combination of CC-01 with an ICI will further enhance the anticancer effect and boost the immune response rate. Collectively, our results support the clin. evaluation of CC-01 in combination with ICIs in several advanced cancers.
Scientific Reports published new progress about 169590-42-5. 169590-42-5 belongs to amides-buliding-blocks, auxiliary class Sulfamide,Immunology/Inflammation,COX, name is 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C17H14F3N3O2S, Application of 4-(5-(p-Tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide.
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