A team led by Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan-Kettering Cancer Center, has shown for the first time the effectiveness of a new technique that could allow the development of more-specific, cell-based immune therapies for cancer. Their findings were reported online today in Nature Biotechnology.
Immunotherapies - which make use of patients' own immune cells that have been augmented in the laboratory - have shown some early success in the treatment of blood cancers including certain types of leukemia. For most cancers, however, cell-based therapies have been harder to develop, in large part because it has been difficult for investigators to train immune cells to specifically attack cancer cells without damaging normal, healthy cells in the body.
The treatment approach, known as adoptive cell transfer (ACT), involves engineering an immune cell called a T cell. In the ACT process, T cells are removed from a patient and a gene is added to allow the T cells to recognize a certain antigen on the surface of a cancer cell. The enhanced cells are grown in the laboratory and then infused back into the patient to seek out and attack cancer cells.
"We are getting better at working with these T cells and enhancing them so that we can get a powerful immunological response against cancer," Dr. Sadelain says. "The dilemma now is that we are concerned with limiting these responses and making them as targeted as possible to avoid potentially harmful side effects."
Cancer cells overproduce certain antigens, which can help T cells to recognize them, but those same antigens are often found in lower levels on healthy cells. "There are very few antigens, if any, that are found only on cancer cells," Dr. Sadelain explains.
"Now we are bringing in a completely new concept," he adds. "If there is no single unique antigen that is found on the surface of the cancer cell we want to target, we instead create T cells that recognize two different antigens found on the tumor cell - a signature that will be unique to that type of cancer - and only attack cells with both antigens, sparing the normal cells that express either antigen alone."