Measles like Complements?? Yeah, they do. Srsly. I'll try to explain.
Last week the news had a story of a woman with bone cancer who was treated with measles virus and "cured." That seems ridiculous, but it actually isn't.
So How Can Measles Treat Cancer?
Viruses were "discovered" so to speak early in the last century. From that time until the last twenty or so years there was speculation that viruses could somehow be modified to treat cancers. In the last twenty years or so the knowledge of now cells are constructed and function at a very detailed molecular level, and advances in technology allow successful attempts to modify viruses to cure rather than kill.
How Measles Virus Edmonston Vaccine Was Born
In 1954 a strain of measles virus was isolated from a patient named Edmonston, and thus named Edmonston B strain.
It was that specific measles strain that was developed as a live non-infective measles vaccine, named MV-Edm. During the process of developing the vaccine the Edm B isolate mutated such that it targeted, as its attachment and entry site, on a cell using a different peptide called CD46 than is used by the wild type measles virus.
So the Edm vaccine mutated and uses a different surface molecule to enter a cell than the wild type does.
An Aside
Our bodies' cells have numerous molecules, such as CD46, protruding out from the surfaces of cell performing a variety of functions. If you could walk across the surface of a human cell it would be a lot more like walking through the industrial parts of, say NYC, than walking across a plowed field in the Texas Panhandle.
For example: the red blood cells may have a large surface molecule that makes them type A or a somewhat smaller version that makes them type B. Those molecules are large enough to be seen by the immune system aka the Complement system, as antigens. If a Type A immune system sees the B molecule on the surface of a transfused RBC, the immune system will attack and destroy that cell.
Back To The Regularly Scheduled Program
The wild type measles virus enters the body via the lymphatic system and would normally infect lymphatic cells. Once it has entered a cell it causes the cell's membrane to fuse to its neighboring cells' membranes causing dysfunction of the tissue and apoptosis. The MV-Edm does the same, except it is introduced by human hands, usually as directly as possible to the site of the tumor.
Who Is CD46? No, not R2D2's brother.
CD46, the membrane peptide, is abundantly expressed on several types of cancerous tumor cells, at the same time being less numerous on healthy cells.
CD46 is present on the surface of the cell membrane on all human cell types except red blood cells. It acts to interrupt the Complement cascade (read as immune reaction or antibody reaction) preventing it from attacking the body's own cells. So it protects our normal cells from being destroyed by our own immune system. (There are autoimmune diseases, "self" attacking diseases, like rheumatoid arthritis.)
Let Me Give You A Complement
The Complement system, aka immune system, is quite fascinating and complex.
It has been way too many years since I studied for that exam and I ain't going there today. (http://www.sanidadanimal.info/...) If you want to see how it works check the link and be amazed. It truly is awesome.
The CD46 protein is a normal cell membrane protein acting in a regulatory function as part of the Complement system. It interrupts the Complement cascade reaction from attacking the body's own cells. It protects "self."
The Complement system is a multistep molecular and cellular process by which the body creates antibodies (A Cells, B cells (the ones HIV attacks), plasma cells, Killer Cells etc.) to what it sees as "foreign", or not "self" and reacts by creating an antibody to that foreign molecule.
So Who is Anti Gin?
An Antigen is anything that stimulates the creation of an antibody. Generically, it is a large complex molecule, 40-50K Daltons or larger, usually a large protein or sometimes a large carbohydrate. It is not the entire bacteria or virus or pollen that stimulates creation of an antibody specific to that organism, It is a single large molecule on the surface of the entity that our body recognizes as "foreign" and reacts to.
This is why when a virus mutates, our system may no longer have resistance to it as the specific molecular structure it needs to recognize on the virus or bacterial surface is altered and not recognizable.
The Complement system also creates a memory of that antibody and of that specific antigen.
There is one Complement pathway for initial exposure resulting in creation of the antibody, and a somewhat different pathway for a subsequence exposure. The reactions are referred to as the Complement cascade as they are a step by step progression of reactions basically unstoppable once initiated.
Back Again To Measles and MV-Edm
Research has been on going for decades to find a way to use infectious viruses to attack tumor tissues.
It had been noticed that occasionally patients with certain types of tumors, who came down with measles, while they had the tumor, showed regression of the tumor and so the MV-Edm vaccine became one of the viruses to be tested for its possible use as a cancer treatment.
MV-Edm is a live virus vaccine with an attenuated non-infective virus, that has been given successfully to over a billion people world wide.
It has been found that MV-Edm virus has oncolytic properties to multiple myeloma and ovarian cancers among other types of tumors. The effect the virus has results in death of the tumor tissue as the measles virus enters a tumor cell, and causes it to fuse with neighboring cells. The virus itself propagates to attack other tumor cells and each effected cell degrades its neighbors creating a fused mass of dead and dying tumor matter leaving surrounding normal tissue unaffected.
So partly by intent, and partly by chance a measles vaccine virus that could no longer infect lymphoid cells and cause measles would instead become used to infect and kill several types of tumor cells.
This is one reason our medical bills are so high, but really. Wow!
I love biological science; it is an incredible four dimensional rabbit warren of wonders and evil villains, vile diseases and parasites, heros, heroines, and minutely crafted miracles,
About that News Article Cure
The news articles last week concerned a woman with bone cancer, who was treated with measles virus. She had/has multiple myeloma, a plasma cell bone marrow cancer. Plasma cells are one of the white blood cells that are part of lymphoid system. They secrete antibodies.
MV-Edm also is selective against non-Hodgkin's lymphoma and well as ovarian cancer and is being tested against a brain tumor that that affects children
More on how MV-Edm works
Measles is an RNA virus. It has two types of glycoprotein that make up its envelope, or outer most covering. One of those, hemagglutinin is responsible for binding to and invading the target cells using the CD46 molecule as its attachment and entry point.
The second glycoprotein is a Membrane Fusion Protein, which is responsible for causing the infected cell to fuse to its neighbor cells forming large multinucleated syncytia that are non-functional, non-cellular, non-living matter.
The CD46 molecule is present in large numbers on the tumor cells of multiple myeloma, a bone marrow cancer, also ovarian cancer, and other cancers in numbers greatly exceeding its presence on normal healthy surrounding tissue.
The body's normal immune system would have difficulty attacking the tumor since the CD46 acts to interrupt the Complement cascade that might attack the tumor cells and destroy them
MV-Edm Can Attack Healthy Cells Too
Obviously, since the MV-Edm is just as capable of attaching to the CD46 sites on normal neighboring cells as well as around the body as a whole, tracking dosage levels is very important.
Through recombinant RNA manipulation the MV-Edm virus can be modified to synthesize a molecule that is nonreactive but detectable in the serum such as the non-reactive peptide MV-hCEA , human carcinoma embryonic antigen.
Also, there have been numerous "tumor markers" identified in recent decades. These are molecules, present in the serum, that are produced either by the tumor cells or the tissues being affected by the tumor and are specific for different types of cancers. They are used as a non invasive means of finding out if there is a cancer and in identifying the type of cancer. Knowing the type also helps identify where the tumor is. So checking for the continued presence of a tumor marker can help in determining if the tumor is still present.
Back To The Syncytia And Other Problems
The tumor cells, once infected, function as host to the virus and become the site of viral replication. As the tumor cells multiply so do the MV-Edm and its effect of degrading the cellular integrity of the tumor.
However as the tumor cells die the MV-Edm lose access to the cells they need for propagation. This may cause a dynamic equilibrium in which the cancer is never completely removed.
It may be possible to genetically engineer the MV-Edm to be more oncotoxic.
Another potential problem may be the immunity of patients, who already have measles' antibody through having had measles or having had the vaccine, and who are capable of destroying the MV-Edm virus before it can affect the tumor.
Thus far that has not proven to be a significant problem. Increasing dosages of the MV-Edm may be sufficient to deal with this issue.
The cancers the MV-Edm are being tested against all occur in compartmented areas of the body like the peritoneal cavity or the bone marrow, so concentrations of the MV-Edm can be introduced in large enough levels to be effective and at the same time be relatively protected from the patient's antibodies. Since the sites are somewhat contained the MV-Edm is less likely to dilute into other parts of the body.
The End
This is research that is still on going. Other viruses are being looked at for their specificity to certain types of cancers that may express other potential attachment sites than CA46.
I know this screed got very long winded but I find this type of bio-whateverness totally fascinating and wicked cool.