CTL019, a clinical trial of T cell therapy for patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL), has shown exciting early results for the first patients to be treated.
This clinical trial, formerly referred to as CART19, uses immune cells taken from a patient's own blood, called T cells. These cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells. Here is how CTL019 works:
While the numbers of patients treated so far are small — 10 adults with chronic lymphocytic leukemia (CLL), and 2 children with acute lymphoblastic leukemia (ALL) — scientists at The Children’s Hospital of Philadelphia and the University of Pennsylvania have been able to show:
Scientists at The Children’s Hospital of Philadelphia and the University of Pennsylvania are very hopeful that CTL019 could in the future be an effective therapy for patients with B cell cancers. However, because so few patients have been treated, it is critical that more adult and pediatric patients are enrolled in the study to determine whether a larger group of patients with B cell cancers will have the same response.
These results were published online by The New England Journal of Medicine on March 25, 2013. It will also appear in the April 18 print issue.
CTL019 is a treatment for children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas, but not other leukemias or pediatric cancers. ALL is the most common childhood cancer. T cell therapy is an option for those patients who have very resistant ALL.
Roughly 85 percent of ALL cases are treated very successfully with standard chemotherapy. For the remaining 15 percent of cases, representing a substantial number of children in the United States, chemotherapy only works temporarily or not at all. This is not a treatment for newly diagnosed leukemia, only for patients with leukemia that has come back (relapsed) who will not benefit from additional chemotherapy or cannot go to bone marrow transplant.
It is important to note that while early results of this treatment are encouraging, it is still very early in testing and that not all children who qualify for the trial will have the same result.
Review the following options for contacting CHOP about CTL019.
Referring physicians and families are encouraged to consider the potential benefits of clinical trials early in the cancer treatment process. In the case of CTL019 and other cell therapies, it is critical that cells are collected from the patient before they are too sick. Also, intensive chemotherapy will decrease the number of normal T cells we need to collect from the patient.
While most childhood cancers are cured by standard treatment protocols, learning about the many new experimental therapies available at CHOP soon after diagnosis may keep more options open for patients who relapse.
Dr. Stephan Grupp leads CTL019 efforts at The Children’s Hospital of Philadelphia. His research builds on an ongoing collaboration with the team that originally designed the CTL019 cells as a treatment for B cell leukemias, and first used the cell therapy against chronic lymphocytic leukemia (CLL) in adults.
Carl H. June, MD, of the Perelman School of Medicine at the University of Pennsylvania, led the research group that announced unprecedented results in August 2011 in treating 3 adult patients with advanced cases of CLL. As of the new publication a total of 12 adult and pediatric patients have been treated using CTL019 cells, 9 patients have responded, and 5 (including two children with ALL) experienced a complete remission.
Dr. Grupp and his colleagues adapted the CTL019 treatment to combat ALL, the most common childhood cancer.
Discover Magazine listed the CTL019 trial as one of the top 10 stories of 2011.
The CTL019 therapy represents a new approach to cancer treatment called immunotherapy or cell therapy. The idea behind immunotherapy is to use our bodies’ own immune cells, which fight infection, to kill off cancer cells.
Cancer researchers have spent more than a decade studying immunotherapy as a possible treatment for cancer. Over the years they solved many of the problems associated with this type of treatment, including learning how to induce the cells to recognize cancer and how to grow cells in a lab in way that it would be safe to re-infuse them into patients.
The final hurdle in this research was the most difficult to jump: learning how to engineer a cell that would continue to grow in the body for more than a few days, and then remain in the body for an extended period of time to continue controlling a patient’s disease for the long-term. CTL019 reflects a solution to this last problem, making the trial unique compared to earlier forms of cell therapy.
In using CTL019 cells to treat his first pediatric patient, Dr. Grupp found that the very activity that destroyed leukemia cells also stimulated a highly activated immune response called cytokine release syndrome. The child became very ill and had to be admitted to the intensive care unit.
Dr. Grupp and his team decided to counteract these toxic side effects by using 2 immunomodulating drugs that blunted the overactive immune response and rapidly relieved the child’s treatment-related symptoms. These results were effective enough that this approach is now being successfully incorporated into CTL019treatments for adults as well.
Dr. Grupp presented an abstract describing this treatment of CTL019-associated cytokine release syndrome at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2012.
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