Challenge of patient bone marrow biopsies with Coxsackievirus A21 for 48 hours resulted in specific purging of up to 98.7% of CD138+ plasma cells without significantly decreasing progenitor cell function.
Does Coxsackievirus A21 target and destroy multiple myeloma cells in vitro and in patient bone marrow biopsies?
Coxsackievirus A21 demonstrates potent and specific oncolytic activity against multiple myeloma cells in vitro and ex vivo, suggesting potential as a systemic therapy or for ex vivo purging prior to stem cell transplantation.
Oncolytic viruses are attractive biological agents for the control of human malignancy. This study assessed the capacity of Coxsackievirus A21 (CVA21) to target and destroy multiple myeloma (MM) and precursor aberrant plasma cells in vitro using established MM cell lines and 15 patient bone marrow (BM) biopsies n = 10 MM and five monoclonal gammopathy of undetermined significance (MGUS). Cell surface analysis revealed that all tumour cells lines expressed high levels of intercellular adhesion molecule-1 (ICAM-1) and decay-accelerating factor (DAF), the receptor molecules to which CVA21 can bind, leading to subsequent cell-entry and infection. MM cell lines were remarkably susceptible to CVA21 lytic infection, producing 100-1000-fold increases in viral progeny within 24 h. In contrast, normal peripheral blood cells were refractile to CVA21 infection. Furthermore, challenge of patient BM biopsies with CVA21 for 48 h resulted in specific purging of up to 98.7% of CD138+ plasma cells, with no significant decrease in progenitor cell function. Data generated in this study suggests that CVA21 virotherapy may have potential applications as a systemic anti-tumour agent for MM, or in the ex vivo purging of malignant plasma cells prior to autologous stem cell transplantation.
Au et al. (Fri,) conducted a other in Multiple myeloma and monoclonal gammopathy of undetermined significance (n=15). Coxsackievirus A21 (CVA21) vs. Normal peripheral blood cells / progenitor cells was evaluated on Purging of CD138+ plasma cells in patient bone marrow biopsies. Challenge of patient bone marrow biopsies with Coxsackievirus A21 for 48 hours resulted in specific purging of up to 98.7% of CD138+ plasma cells without significantly decreasing progenitor cell function.