Project Spotlight

Our faculty are conducting research that leads to breakthroughs in cancer research. Their findings are publicized in high-impact journals, news media and textbooks.

A Novel Bispecific CD38 Antibody to Target Multiple Myeloma
Led by Damian Green

Dr. Green

Multiple myeloma is an incurable cancer of a specific cell found only in the bone marrow. Normally these cells, called plasma cells, are responsible for helping people fight off infections. When they become cancerous, plasma cells no longer function normally and start to behave in an uncontrolled manner. They fill up the bone marrow with useless clones of themselves and also can release large amounts of “junk” material. The cancerous plasma cells and the “junk” they produce can cause damage to bones, kidneys and other important organs and tissues.

Greater than 100,000 Americans are affected by multiple myeloma and 26,850 new cases are diagnosed each year. New treatments have significantly improved outcomes for patients, who are now living an average of seven years from their diagnosis, but despite exciting advances almost all patients eventually die from the disease. Current approaches can work temporarily, but do not cure the disease.

We have learned that multiple myeloma cells are very sensitive to radiation. The problem is that the disease is found in too many locations throughout the body and radiation also damages normal cells in their path.  It would require too much radiation to get to all the myeloma sites. Over the last few years we have discovered new ways to specifically target cancer cells in the body. One very promising way is to use antibodies. These antibodies are developed to specifically attach to the cancer cells when injected into patients. After they attach, the antibodies cause the patient’s immune system to attack the cancer cells. This works pretty well in some cases, but usually does not cure patients because the antibodies can’t get to every cell and some of the cancer cells escape, regroup and spread again. These hold-out cells can also develop resistance to treatments over time.

The research proposed in this project takes advantage of how sensitive the multiple myeloma cells are to radiation and uses what we have learned about antibodies. We can use antibodies to bring very small radioactive particles into direct contact with the multiple myeloma cells to kill them while not causing damage to normal cells. We call this radio-immunotherapy. With this approach not every cell needs to have the antibody attach to it, because the radiation can also kill cancer cells that are close by. To get the radiation to the cancer cells we have designed a special type of antibody that we call bi-specific. This means it has two arms; one arm is designed to grab the cancer cells and the other arm grabs the radiation. We inject the antibody into patients and let the first arm attach to the cancer cells, then we inject the radioactive particles and the second arm attaches onto those. In this way we get the radiation to go only to the cancer cells. Fortunately these radioactive particles are so small that if they are not grabbed by the bispecific antibody’s radiation arm, they will be cleared out of the body within minutes. We call the whole process tumor pre-targeting. The type of radioactive particles we use only do damage to cells that are very close to them, and especially to cancer cells, so other normal cells are spared. We have already shown that this approach can work in animal models of multiple myeloma, we can cure mice. People are more complicated and we are working to refine the treatment to make it work better in human patients. It is important to remember that we cannot be satisfied if any of the cancer cells escape and our approach is designed to deliver radiation to every single one of them. We believe that is the only way to cure patients.