Rituxan® and Beyond: Antibodies As Magic Bullets in Cancer Therapies
Antibodies are proteins that our immune systems use to help fight infections. When viruses infect a cell, virus-specific molecules are displayed on its surface; these are recognized as abnormal by certain immune cells (called B cells), which then make antibodies that specifically bind the viral molecules on the infected cells.
Sometimes, antibody-binding is enough to trigger infected cells to die. Sometimes, other immune cells, including natural killer (NK) cells, can be drawn in by the antibody to attack and kill the infected cells. In both cases, the spread of infection is blocked by antibody-directed killing.
Since cancer cells also display abnormal proteins, researchers realized that antibodies might be used to fight cancer. They began developing antibody "magic bullets" needed to win this war. Rituximab (Rituxan) - the first antibody approved by the U.S. Food and Drug Administration (FDA) for treating cancer - recognizes a protein called CD20. It was approved in 1997 for the treatment of patients with relapsed follicular lymphoma, a form of B-cell non-Hodgkin's lymphoma (B-NHL). Rituxan is now widely used as an effective and safe front-line treatment for follicular lymphoma patients and is used in combination with chemotherapy for patients with follicular and other forms of B-NHL.
A radioactive form of Rituxan called tositumomab (Bexxar®) can be even more effective for B-cell lymphoma patients because it carries lethal radiation directly to lymphoma cells. Society-funded researchers, including Oliver Press, M.D., recently showed that Bexxar can be safely used to kill lymphoma cells before stem cell transplantation in patients with relapsed or refractory B-cell NHL who are too old or infirm to tolerate standard high-dose chemotherapies.
Chronic lymphocytic leukemia (CLL) is another cancer that frequently displays CD20. Society-funded researcher John Byrd, M.D. and his colleagues recently found that Rituxan can be a safe and effective treatment for previously untreated CLL patients when used in combination with the drugs pentostatin and cyclophosphamide. Even CLL patients with poor risk factors that made them unlikely to benefit from standard chemotherapies showed good responses to this novel combination.
Alemtuzamab (CamPath®) is an antibody that binds a different protein called CD52. Campath is already FDA-approved for patients with relapsed or refractory CLL, and may also be effective for patients with B-cell lymphomas. Society-funded investigators Margaret Shipp, M.D., Jeffery Kutok, M.D., Ph.D. and their collaborators recently analyzed samples from 294 leukemia and lymphoma patients and found that the vast majority of low-grade and precursor B-cell leukemias and lymphomas display CD52, whereas fewer of the aggressive B-cell cancers, T-cell cancers, myeloid leukemias and multiple myelomas are CD52 positive. They recommend that the test they used in their study be used to identify patients who may most benefit from CamPath treatments.
Campath, Bexxar and Rituxan may not be helpful for multiple myeloma patients because myeloma cells express little if any CD20 or CD52, but still other antibodies are being developed for these patients by Society-funded researcher Giovanni Tonon, M.D., and others. And Roland Walter, M.D. is funded by the Society to determine how to make the anti-CD33 antibody, Gemtuzumab ozogamicin (Mylotarg®) useful for more patients with acute myeloid leukemia (AML). Mylotarg is already approved for treating relapsed and refractory AML.
Deborah Banker, Ph.D.