CD24 Tumor-Initiating Cell as a Novel Therapeutic Target in Myeloma
Abstract
Multiple Myeloma (MM) is a blood cancer of the B cell lineage characterized by monoclonal plasma cells. Despite the recent advances in therapy myeloma remains incurable and accounts for 19% of deaths from hematopoietic malignancies. Most patients initially respond to the therapy but nearly all relapse and become refractory to treatment. These observations suggest that the persistence of a tumor cell population with very low proliferative capacity and very limited sensitivity to our most intensive therapies in myeloma. These myeloma cells, which escapecurrent modes of therapy, are named tumor-initiating cells (TICs) in myeloma. Understanding the nature of myeloma-TICs will provide an opportunity to cure this disease by preventing its relapse. Through a systematical screening, our studies presented here demonstrated that CD24+ myeloma cells maintain the features of self-renewal and drug resistance in myeloma. To further determine CD24 as a biomarker in clinical myeloma samples, we will add myeloma cell markers, such as CD38+CD45, to exclude non-myeloma cells for studying CD24+ primary myeloma cells. We predict that myeloma patients with high percentage of CD38+CD45CD24+ myeloma cells will be relapsed rapidly and die early, and anti-CD24 antibody may eliminate myeloma tumor initiating cells resulting in cure of myeloma disease or significant extension of patient survival. Therefore, this proposal will focus on validating CD38+CD45CD24+ as TICs marker and its potential therapeutic role using primary myeloma samples. The first aim will determine the CD38+CD45CD24+ phenotype in maintaining stemness and its clinical relevance in primary myeloma samples. In the second aim, tumor initiating characteristics of CD38+CD45CD24+ cells will be determined using in vitro and in vivo myeloma mouse models. In the third aim, we will investigate the efficacy of humanized CD24 antibodies in killing myeloma tumor-initiating cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1117002
Entities
People
- Gail A Bishop
Organizations
- University of Iowa