CD46 is a receptor for many viruses and is the main receptor for the vaccine strains of the measles virus (MV). CD46 expression is related to what goes on in the the bone marrow microenvironment, affects important messaging pathways and can also impact the gain of 1q in myeloma.
The researchers confirmed the role of CD46 by blocking CD46 expression on a percentage of the cells. When they blocked the CD46 expression and administered the measles vaccine, it reduced cell death by more than 90%.
Importantly, they found that early myeloma conditions like MGUS have higher levels of CD46 as compared to normal plasma cells.
They also found that:
CD46 expression level in primary cells was high in myeloma cells but not significantly different between samples with or without del(17p). CD46 expression might also be increased independently of p53 because of chromosome 1q amplification.
The authors conclude that the measles vaccine could be particularly effective for patients with the del17p (with a loss of TP53), but note that it should be used with caution depending on the immune status of the patient.
Association of TP53 deletion with mutation is frequent in high-risk MM (especially in extramedullary disease) and is well known to be associated with a low response rate to therapies. Thus, the Measles Vaccine is an attractive tool to target p53-deficient myeloma cells, for which no efficient therapies are available yet. The major concern is preexisting immunity and/or the impossibility of repeating viral injections in MV-naive patients. Although the vaccine MV strain has proven its safety in billions of people for more than 30 years, the virus load for cancer treatment is up to 106 higher than for vaccination. When inoculated with billions of viral particles, patients became febrile, hypotensive, and tachycardic, with severe nausea and vomiting.
They state that myeloma cells that are p53 deficient are highly responsive to the measles vaccine and that a study should be created to test this for patients with the TP53 loss.