Hijacking the same sorts of viruses that cause HIV and using them to reprogram immune cells to fight cancer sounds like stuff of the future.
Some scientists believe that the future is closer than we think – and are now studying the approach in clinical trials at City of Hope. Immunotherapy is a promising approach for cancer treatment, and while the science is quickly advancing, the idea isn’t exactly new.
In the late 1800s – before much was known about the immune system – William Coley, M.D., a New York surgeon, noticed that getting an infection after surgery actually helped some cancer patients. So he began infecting them with certain bacteria, with positive results.
Today, doctors continue to seek ways to harness the immune system to fight disease. City of Hope researchers are examining immunotherapy techniques to treat some of the toughest cancers including gliomas, ovarian cancer and hematologic cancers. One especially promising approach is called adoptive T cell therapy.
Leslie Popplewell, a physician and associate clinical professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, recently completed one clinical trial on adoptive T cell therapy, is wrapping up another and has just embarked on a third. All her studies thus far have been in patients with B cell non-Hodgkin lymphoma – a cancer that affects the body’s B cells, which are immune cells that secrete antibodies.
“It’s exciting and there have been really nice responses in patients who have really aggressive cancer,” she said. “I think it’s generally recognized in the medical community that this is a hot new therapy – and it’s brought some people back from the brink of death. Not that many centers are doing these trials right now, so it’s really exciting to be part of the few that are doing this.”
While immunotherapy has been a medical dream for a while, new developments in pharmaceutical science have helped make the necessary cells and viral vectors needed to study and administer immune therapies more accessible.
Participants in Popplewell's adoptive T cell therapy research have all been candidates for autologous stem cell transplants, that is, transplants using their own stem cells. Here's how it works:
Patients are prepared for their transplants with chemotherapy – the standard routine for these transplants. However, they also have a few extra steps. Their T cells are extracted, and then more of their own T cells are grown in a lab. Those T cells are tweaked with the help of a lentivirus, from the same family of viruses as HIV. These retroviruses have no disease-causing ability, but retain their ability to do what they does best: Invade cells.The first adoptive T cell therapy trial with a handful of patients was designed to test safety and efficacy. Preliminary results look good so far, Popplewell said. In the second study, the same basic procedure was used, but the T cells were given an extra molecule to help augment the immune response and potentially spur the immune system to mount an attack against any returning cancer more quickly. In the study just beginning, the formula for the T cells has been adjusted so that the cells are optimized to attack to the Y-shaped receptors they are trained to recognize.
Only now the virus is programmed to retool the T cells so they are sensitive to a molecule called CD-19, which is found on the surface of lymphoma cells. The hope is that the immune cells will spring into action and begin fighting the cancer as soon as the CD-19 is detected. (Learn more about adoptive T cell therapy in this question-and-answer interview with Popplewell.)
For the study patients, the stem cell transplants are potentially cures on their own, but because this kind of lymphoma is prone to relapse, augmenting it by giving their own immune systems and extra boost could ward off recurrences, Popplewell said.
Learn more about hematologic cancer treatment at City of Hope.
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