Development of LILRB1-based immunotherapy for multiple myeloma treatment
Alec Zhang
PhDThe University of Texas Southwestern Medical Center
Project Term: July 1, 2021 - June 30, 2024
LILRB1 is a human immune inhibitory receptor expressed on a variety of immune cells. Based on preliminary data, we hypothesize that blocking LILRB1 signaling in immune effector cells of myeloma patients will lead to increased anti-cancer activities of immune cells. We will identify subsets of myeloma patients with higher LILRB1 expression on immune cells, and determine whether anti-LILRB1 antagonizing antibodies can improve the function of immune cells for multiple myeloma treatment.
Multiple myeloma is the second most common blood cancer in the United States. The 5-year survival rate for people with multiple myeloma is about 50%. Although novel medications have improved overall response rates and survival of the patients in the past two decades, many patients only respond partially to existing treatment and eventually develop treatment resistance. New therapies with improved efficacy and decreased toxicity are needed. LILRB1 is a protein antigen that is widely expressed on different human immune cells and inhibits the immune responses. In our pilot study, we found higher LILRB1 levels on certain immune cells from multiple myeloma patients with persistent disease after treatment, compared to those patients with minimal disease. We also detected an increase of LILRB1 levels in myeloma patients after treatment of lenalidomide, a drug commonly used in myeloma treatment. We developed specific anti-LILRB1 antibodies and found that the antibody treatment increased the function of a special type of immune cells against multiple myeloma development. We hypothesize that inhibition of LILRB1 signaling in immune cells of myeloma patients will lead to increased immune activation and improve the anti-myeloma outcome. To test this hypothesis, we will identify which subsets of myeloma patients have higher LILRB1 levels on various types of immune cells, and study the relationship between LILRB1 expression and patient characteristics including disease stage, mutation status, and treatment history and response. Next we will determine whether anti-LILRB1 antibodies can improve the anti-myeloma function of different types of immune cells. In parallel, we will evaluate the potential toxicity of anti-LILRB1 antibodies to normal human blood cells. Our study will significantly improve our understanding of interplay between myeloma cells and immune cells, and may lead to development of novel anti-myeloma immunotherapies.