Leukemia patients who received infusions of their own T cells, after the cells had been genetically engineered to fight the patients’ cancerous tumors, reacted to the therapy in a positive way, staying in full remission for over two years.
The new therapy was developed by a group of scientists from the Perelman School of Medicine at the University of Pennsylvania and the results will be presented at the American Society of Hematology’s Annual Meeting and Exposition.
Participants in this clinical trial all had advanced cancers, including 10 adults with chronic lymphocytic leukemia and two children with acute lymphoblastic leukemia. Patients were treated at the Hospital of the University of Pennsylvania (HUP) and the Children’s Hospital of Pennsylvania (CHOP).
Of the first three patients, two were treated with the therapy at HUP and stayed healthy and in remission even after two years following their treatment, and the engineered cells were still present in their bodies. The scientists’ findings showed the first effective and sustained example of the use of gene transfer therapy to change the body’s own immune cells into forces focused on battling cancerous tumors.
Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in Penn’s Abramson Cancer Center, says:
“Our results show that chimeric antigen receptor modified T cells have great promise to improve the treatment of leukemia and lymphoma. It is possible that in the future, this approach may reduce or replace the need for bone marrow transplantation.”
The findings act as a stepping stone on a new pathway of treatment for these kinds of blood cancers, which in late stages have the potential to only be cured by bone marrow transplants. Bone marrow procedures come with a 20 percent risk of death, as well as a long hospital stay, and only give a small chance of cure to patients whose disease has not had any changes from other treatments.
The new treatment was conducted first by removing patients’ cells through an apheresis process somewhat like donating blood, and then altering them in Penn’s cell and vaccine production facility. The patients’ T cells were modified to aim at tumor cells through a gene alteration method using a HIV-derived lentivirus vector. The vector encodes an antibody-like protein, known as a chimeric antigen receptor (CAR), which is made to bind to a protein called CD19 and is seen on the surface of the T cells.
The changed cells then get reintroduced to the patients’ body after lymphodepleting chemotherapy. The T cells start expressing the CAR and then aim all of their power at killing cells that express CD19 (CLL, ALL tumor cells and normal B cells). The changed T cells ignore all other cells that do not express CD19, which cuts down on side effects normally experienced during classic therapies.
Not only do they kill cancer cells, the T cells that express the CAR also prompt the cell to create cytokines that encourage other T cells to multiply, making a larger group until all the targeted cells within the tumor are eliminated.
In those patients who had complete remissions following treatment, the CAR T cells showed extreme reproduction after infusion, with the most active expansion taking place between 10 and 31 days after infusion. All of these patients experienced a cytokine release syndrome with symptoms including nausea, fever, hypoxia, and low blood pressure. The syndrome was treated using tocilizumab.
Notably, the T cell treatment successfully eliminated great amounts of tumor in these patients.
According to the results, patients with total responses demonstrated that normal B cells were killed along with their tumors. As a preventive step, patients received regular gamma globulin treatments because these cells are crucial for the body’s immune system to fight infection. No irregular infections were seen.
Written by Kelly Fitzgerald