Leronlimab Inhibits Colon Carcinoma Metastasis in a Humanized Mouse Xenograft Model

Leronlimab, a humanized monoclonal antibody directed to the CCR5 receptor, demonstrated anti-tumor activity in humanized NSG mouse models of both heterotopic and orthotopic SW480 human colon carcinoma. The anti-tumor effect was lost in non-humanized mice, suggesting a critical role for engrafted human leukocytes. Development of xGVHD was delayed in both tumor-bearing and non-tumor-bearing mice that had been treated with leronlimab. Leronlimab induced human CD4+CD25+ cells in the peripheral blood of tumor-bearing (1.5-fold increase, p=0.016) and non-tumor-bearing animals (2.2-fold, p=0.0038). Leronlimab reduced CD4+CD25- cells (1.84-fold reduction, p=0.033). In the orthotopic colon cancer model, lung metastatic burden was decreased ~87% in leronlimab-treated mice compared to IgG-treated animals (p=0.012). Blockade of CCR5 signaling reduced peri-tumoral vessel formation feeding the tumor, 62% (p=0.013). As CD4+CD25+ T cells, play a crucial role in immune checkpoint inhibitor (ICI) responses we assessed CCR5/immune checkpoint gene expression in human colon cancer. CCR5 and its ligands were overexpressed in human colon cancer, correlating with increased immune checkpoint gene expression in both microsatellite stable (MSS) and instable (MSI) patients.