Sophie Sloan
Research Mentor(s): Mikel Gurrea Rubio
Mentor Department: Internal Medicine – Rheumatology
Authors: Sophie Julia Sloan, Mikel Gurrea-Rubio, David A. Fox
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 15
Abstract
This research is being performed to better understand the efficacy and efficiency of UMCD6, an anti-CD6 monoclonal antibody developed in our lab, to target breast cancer stem cells (BCSCs). CD6 is a cell surface protein exclusively expressed by T cells and NK cells. CD6 plays a central role in the generation of autoimmunity. In both CD6-/- mice and CD6-humanized mice treated with UMCD6, striking reductions in Th1/Th17 responses and clinical signs of autoimmunity are observed. Soon after we identified CD318 (also known as CDCP1) as a new ligand of CD6, we began efforts to understand the role of the CD6/CD318 axis in anti-tumor immunity. We have recently demonstrated that UMCD6 increases CD318+ breast cancer cell death by activation of cytotoxic lymphocytes far more efficiently than control antibodies and checkpoint inhibitors that interrupt the PD-1/PD-L1 axis, both in vitro and in vivo. Because BCSCs are responsible for recurrence and metastasis of tumors, we have recently tested the efficacy of UMCD6 to enhance human lymphocytes to kill these cells. First, we assessed the expression of CD6 ligands on BCSCs by flow cytometry. We found that the CD6 ligand CD318 co-colocalizes with BCSCs (gated as ALDH+/CD2-/CD44+ cells), meaning that BCSCs express CD318. Next, we tested the effects of interrupting the interaction between CD6 and CD318 with UMCD6 on the ability of lymphocytes to kill the BCSCs. Co-culture experiments using a multiplexed time-lapsed imaging system showed robust enhancement of breast cancer cell death in the presence of human lymphocytes and UMCD6, which was more pronounced than that generated with pembrolizumab (anti-PD-1). In addition, flow cytometry analyses for ALDH enzymatic activity in BCSC lines co-cultured with human lymphocytes revealed a statistically significant decrease in BCSC frequency in the presence of UMCD6. Our preliminary data now demonstrates that UMCD6 enhances the ability of human lymphocytes to kill breast cancer stem cells in vitro.
