WASHINGTON --Antibodies, once touted as the "magic bullets" of cancer care, are now fulfilling that promise and more advances are on the way, say cancer researchers at the Georgetown Lombardi Comprehensive Cancer Center
In a review article posted online March 16 in Cell, the researchers say that refinements and modifications of monoclonal antibody drugs -- several of which have already revolutionized the care of breast and colon cancer --are now being tested in most tumor types.
These modifications allow antibody drugs to bind to more than one target on a cell, and to directly stimulate the body's immune response to promote vaccine-like antitumor effects. Others have been designed to boost their killing power by carrying a payload of radiation, toxins, or other chemicals.
'We are heading into an era where antibodies will not just be components of an effective therapeutic strategy, they will be at the core of an oncologist's treatment plan for patients," says the review's lead author, Louis M. Weiner, M.D., director of Georgetown Lombardi Comprehensive Cancer Center, an internationally recognized expert in immunotherapy research.
"Advancement in antibody cancer treatment is not a minor advance or a trivial victory. This is big time stuff," Weiner said in an interview.
His co-authors on the review are Joseph Murray and Casey W. Shuptrine, both graduate students in the Tumor Biology Training Program at Georgetown Lombardi.
A good example of the new class of antibody-based therapies is ipilimumab, a drug approved in 2011 to treat patients with metastatic melanoma, says Weiner. Ipilimumab is a fully human antibody which binds to an immune antigen (CTLA-4) on cancer cells that transmits a signal inhibiting other immune cells from destroying the tumor. Ipilimumab blocks CTLA-4, thereby inducing an active immune response.
"This agent turns off the brakes of an immune response against melanoma, liberating the body to set up long term protectiion against the cancer," Weiner says. "About 10 percent of patients with metastatic melanoma who use it go into long-term remission, and may well be cured."
Antigens are substances, often a cell surface receptor, which causes the immune system to produce an antibody against it, as a way to target and kill the cell. Therefore, antibody agents targeted to a receptor on a cancer cell have the unique capacity to target and kill cancer cells while activating an immune response. A monoclonal antibody (mAb) is an artificially produced antibody designed to bind to a specific cancer antigen, and currently 11 mAbs are approved for use in oncology, Most of these were approved in the last decade. The most commonly used are trastuzumab (Herceptin) to treat HER2-positive breast cancer and rituximab (Rituxan) for specific forms of lymphoma and leukemia.
Advanced antibody engineering techniques are being used to create more effective treatments, Weiner says. One group, known as bispecific antibodies (bsAbs) can bind to two different tumor antigens, or to a tumor antigen and another target in the tumor microenvironment, such as an immune system killer cell. Other mAbs are being designed as "conjugates" to carry a toxic payload, which can be a radionuclide, other drugs, toxins, or enzymes. Researchers are also now increasing the capacity of antibodies to be absorbed by cancer cells so that they can bind to antigens inside the cell – not just on the outside of the cell surface.
"The field of cancer antibodies is definitely maturing. There are scores of new cancer antibody agents now being tested in virtually every kind of solid cancer, and oncologists, researchers and pharmaceutical companies are excited about their promise," Weiner says. "To me this is like watching a child grow up and do well -- very well -- in young adulthood."
The work was supported by funding from the National Cancer Institute. Weiner serves as an expert consultant on cancer immunotherapy to several pharmaceutical companies, none of whose products are mentioned in this article.
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 40 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health. In fiscal year 2010-11, GUMC accounted for 85 percent of the university's sponsored research funding.
Journal
Cell