UMCD6 (anti-CD6) Enhances Peripheral Blood Mononuclear Cells to Kill Breast Cancer Stem Cells – UROP Spring Symposium 2022

UMCD6 (anti-CD6) Enhances Peripheral Blood Mononuclear Cells to Kill Breast Cancer Stem Cells

photo of presenter

Camila Amarista

Pronouns: she/her

Research Mentor(s): Mikel Gurrea Rubio
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine – Rheumatology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 3 – 1:40pm – 2:30 pm
Room: League Ballroom
Authors: Camila Amarista, Mikel Gurrea-Rubio, David Fox
Presenter: 77

Abstract

This research is being performed to better understand the efficacy of UMCD6, an anti-CD6 monoclonal antibody, to enhance cytotoxic lymphocyte activity against breast cancer stem cells. CD6 is expressed by virtually all T cells and 60% of human NK cells. Interrupting CD6-CD318 interaction with UMCD6 1) reduces Th1- and Th17-driven autoimmune responses in autoimmune mouse models of multiple sclerosis, rheumatoid arthritis and uveitis and 2) concurrently activates cytotoxic lymphocytes (NK cells and CD8+T cells) to kill a wide range of CD318+ cells cancer cells. Particularly, UMCD6 increases cancer cell death and lowers cancer cell survival more robustly than checkpoint inhibitors that interrupt the PD-1/PD-L1 axis or anti-CD318, in breast, lung and prostate cancers. In vivo, UMCD6 also augments Peripheral Blood Monocular Cells (PBMC) and NK killing of human breast cancer cells xeno-transplanted into immunodeficient scid/beige mice. Current Immune Checkpoint Inhibitors (ICI) present two big challenges: appearance of clinical manifestations of autoimmune-like/inflammatory side effects and resistance of cancer stem cells to lymphocyte killing. Because cancer stem cells are responsible for recurrence in many cancers including breast, we have tested the efficacy of our antibody to enhance human lymphocytes to kill these cells. First, we assessed the expression of the CD6 ligand CD318 on SUM159 cells by flow cytometry. We then set up immune killing assays using human PBMCs pre-incubated with UMCD6 or an antibody control, in co-cultures with breast cancer stem cells. In an IncuCyte apparatus, we measured the number of tumor cells that underwent apoptosis for five days. Our preliminary data now demonstrates that UMCD6 is effective in killing the breast cancer stem cell line SUM159.

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Biomedical Sciences, Interdisciplinary

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