Questions continue to pour in about measles virotherapy, which I wrote about in my May 22, 2014 blog here. Myeloma patient and advocate Jack Aiello raised an interesting question: "If the massive 100-billion dose of engineered measles (MV-NIS) virus is destroying myeloma, why isn't it also causing a raging case of measles?"
Dr. Stephen Russell of the Mayo Clinic took the time to provide the highly technical answer, which I will do my best to explain. (I have also created a graphic, FIGURE 1, which I hope will help.)
First of all, it must be emphasized that the measles virus used as the starting point for these research studies was the attenuated strain, the weakened strain used for measles vaccination. This strain has proven to be very safe with very limited potential to ever actually cause measles.
The next step was to take this weakened strain and "morph" it in a different way by growing it on human cancer cells. Viruses need the machinery of a cell to survive. In this case, the measles virus adapted to growing in cancer cells. A main adaption was to use a surface receptor called CD46 to enter the cell.
It turns out that myeloma cells have many CD46 receptors, whereas normal cells have very few: a 10-fold difference. Myeloma cells infected with virus also develop a "measles attachment protein" on their surface. This leads to the development of large clumps (called syncytia) of joined and fused myeloma cells which subsequently die. Another factor which helps speed up this myeloma cell destruction is that internal cell defenses are not triggered since the engineered measles virus lacks the critical pieces of C and V proteins which normally trigger the defenses.
So there you have it: selective binding and uptake into myeloma cells, and rapid reproduction of virus because of weakened defenses within the cell.
The opposite is the case with normal tissues. First of all, measles virus is attacked by antibodies in the blood stream (abundant normally after vaccination, but low-to-zero in half of myeloma patients). Then, there is very limited access to normal tissues which have few CD46 receptors. Plus, when virus does enter, internal anti-viral defenses are high and able to eliminate entering virus.
In myeloma cells, the "Trojan horse" filled with virus enters the CD46 gateway and takes over. In normal tissues, virus rarely makes it through the gate--and even then the cell is armed and ready. And what about the HeLa cells used to grow up massive batches of the engineered measles virus to treat myeloma patients? Well, these HeLa cells are a culture of cells from cancer of the cervix taken from a woman named Henrietta Lacks more than 60 years ago. The cells grow in a liquefied suspension culture. The engineered measles virus is well adapted to targeting cancer cells.
This is why myeloma cells are attacked and normal cells escape unscathed. It always helps to understand. Let's hope that more patients can benefit from this carefully crafted strategy.
As always, stay tuned!
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