mProX™ Human C5AR1 Stable Cell Line

Zhang C, et al. "C5aR1 blockade reshapes immunosuppressive tumor microenvironment and synergizes ." Oncoimmunology, 2023.
High-grade serous ovarian cancer (HGSC) is infiltrated by immunosuppressive cells like M2-polarized tumor-associated macrophages (TAMs) and regulatory T (Treg) cells, leading to a modest response to monotherapy using immune checkpoint blockade (ICB) targeting PD-1/PD-L1. The C5a/C5aR1 axis plays a role in programming TAMs in solid tumors and shows potential as an immunomodulatory target for treating HGSC. To investigate the relevance of C5aR1 in HGSC, the expression and relationship of C5aR1 with tumor-infiltrating immune cells were examined in a training cohort (n=120) and in fresh HGSC tissues (n=36) using immunohistochemistry and flow cytometry. Transcriptomic analysis of xenografts revealed the mechanisms of PMX53, an orally bioavailable C5aR1 inhibitor, in modulating the immune microenvironment. Therapeutic relevance was confirmed in ex vivo tumor cultures and The Cancer Genome Atlas (TCGA) datasets. C5aR1 expression was found to independently predict a poor prognosis in HGSC and was associated with the immunoevasive subtype characterized by increased infiltration of pro-tumor cells (Treg cells, M2-polarized macrophages, and neutrophils) and suppressed CD8+ T cell activity. PMX53 inhibited tumor growth and improved immunosuppression when combined with aPD-1 in various tumor types. Single-cell RNA-seq analysis showed that TAMs predominantly expressed C5aR1 and had an immunosuppressive-related signature in C5aR1+ TAMs. Additionally, the combination of C5aR1 and PD-L1 was associated with specific molecular characteristics and predicted response to treatment. Therefore, C5aR1 expression levels could serve as a prognostic factor in HGSC, and the incorporation of PD-L1 could serve as a novel biomarker to guide therapeutic decisions.
Pubmed: 37791232   DOI: 10.1080/2162402X.2023.2261242

Fernandes DC, Tambourgi DV. "Complement System Inhibitory Drugs in a Zebrafish (Danio rerio) Model: ." International journal of molecular sciences, 2023.
The dysregulation of complement system activation typically leads to acute or chronic inflammation and can contribute to the development of various diseases. While necessary for innate defense, excessive activation of this system can be harmful to the host. Therefore, the use of drugs to inhibit complement system activation may be crucial in disease therapy. Notably, synthetic peptides Cp40 and PMX205 have been shown to selectively inhibit C3 and block the C5a receptor (C5aR1), respectively. The robust zebrafish (Danio rerio) serves as a valuable model for studying the complement system. In this study, molecular docking interactions were analyzed in silico to determine whether these peptides interact with their target molecules in zebrafish, for subsequent in vivo validation. Our findings suggest that both Cp40 and cyclic peptide PMX205 display favorable interactions with their respective zebrafish targets, supporting the use of zebrafish as an animal model for therapeutic evaluations of these inhibitors.
Pubmed: 37762197   DOI: 10.3390/ijms241813895