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Tough blood cancers are responding to treatment with the patient’s own genetically engineered immune cells, according to a cancer specialist who is helping test the bold — and risky — approach.
The treatment has produced complete remissions in large percentages of patients treated, up to 90 percent in one group of 30 patients. Moreover, these are all extremely sick patients, whose cancer has resisted other therapies, leaving them with virtually no options. The longest survivor has been in complete remission for more than 4 years, said Dr. David Porter of the University of Pennsylvania.
Porter spoke Sunday at the 35th Annual Conference on Clinical Hematology & Oncology, held in La Jolla by Scripps Health. Speakers like Porter came from around the country to discuss advances in their field, part of a continuing medical education program to keep doctors up to date with the latest medical advances. The conference continues through Tuesday.
Porter works with Dr. Carl June and other colleagues to hone the effectiveness of using T cells genetically programmed to attack malignant B cells. B cell malignancies cause such cancers as chronic lymphocytic leukemia, or CLL; acute lymphoblastic leukemia, or ALL, and non-Hodgkin’s lymphoma.
The genetically altered T cells are given an artificially created gene to produce a chimeric antigen receptor. This receptor recognizes the protein CD19, produced almost exclusively on B cells. The T cells hone in on this protein and kill the B cells. When the cancer is knocked down, some of the T cells remain behind, ready to pounce on any recurrence.
The trials are now expanding to include myloma, Porter said. For more information on the university’s T cell-based clinical trials, go to http://www.penncancer.org/tcelltherapy.
June’s team began testing the therapy in 2010 in CLL patients and then in those with ALL. These were all patients with relapsed cancers that had become resistant to other therapies. The therapy has been progressively refined, Porter said. Other centers have developed their own versions of this therapy.
In October, 2014, the University of Pennsylvania and Children’s Hospital of Philadelphia announced that 27 out of 30 patients with relapsed ALL achieved a complete remission within one month of treatment, and 23 were still alive 6 months after treatment. As of October, 19 of the patients remained in remission. Most treated, 25 out of 30, were children. The response rate with CLL is about 47 percent, Porter said.
Powered-up cells
The therapy uses T cells filtered out of the patient’s blood and given a tamed version of HIV that carries the artificial gene that recognizes the receptor. Then the cells are cultured to multiply. When enough cells are made — just how many are needed isn’t yet clear — the cells are re-infused into the patient. If all goes well, the T cells multiply in the patient and kill the B cells.
“Every cell we infuse has the ability to kill between 1,000 and 93,000 tumor cells,” Porter said. “We’ve now shown these cells can persist in vivo beyond four years.”
The ability to keep the engineered T cells alive and thriving in the body is important to long-term cancer control. Even one malignant cell can bring back the cancer. The goal is to get a long-term suppression of the cancer so it doesn’t produce symptoms. It isn’t regarded as a permanent cure.
Some patients don’t respond to the therapy, and doctors are trying to find out why it fails those patients, Porter said. The only reliable indicator is that the re-infused T cells don’t multiply, but doctors would like to find out in advance which patients are likely to respond or not.
The therapy carries dangers, as immune system chemicals called cytokines flood the body and billions of malignant cells are killed. In just a few weeks, 2.5 to 7 pounds of tumor cells are killed in the patients, Porter said. A woman with colon cancer given similarly engineered T cells died from complications, apparently because the cancer had spread to the lungs.
And the concept of using HIV, however tamed, as a delivery vehicle, is problematic to some. In December, doctors at University of Texas MD Anderson Cancer Center reported signs of effectiveness with a non-viral method of producing the chimeric antigen receptor-bearing T cells. Patients with ALL, CLL and non-Hodgkin’s lymphoma were treated.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.