Scanning electron micrograph of a human T-cell lymphocyte (National Institute of Allergy and Infectious Diseases, NIH)
8 December 2015. Two clinical trials of personalized immune cells to treat blood-related cancers — acute lymphoblastic leukemia in children and non-Hodgkin lymphoma in adults — showed high rates of response and remission. Results of the two trials, conducted by University of Pennsylvania medical school, were reported earlier this week at a meeting of American Society of Hematology in Orlando.
The trials tested a therapy derived from an individual’s own immune system cells, modified to seek out and destroy cancer cells in that person’s blood. The therapy, code-named CTL019, starts with a sample of an individual’s blood cells and separates out T cells, white blood cells used by the immune system to fight invading pathogens, then reprograms the T cells with genetic engineering to find and kill cancer cells.
The engineered T cells become hunter cells, containing a protein known as chimeric antigen receptor that acts like an antibody. These hunter cells are infused back into the patient, seeking out and binding to a protein called CD19 found on the surface of B cells — another type of white blood cell — associated with several types of blood-related cancers. Among the properties programmed into CTL019 is the ability of hunter cells to quickly multiply and accumulate to battle the cancerous cells.
One study tested CTL019 with relapsed or unresponsive acute lymphoblastic leukemia, led by Penn pediatrics professor Stephan Grupp, which recruited 59 children with a median age of 11 years. Acute lymphoblastic leukemia is a cancer of blood and bone marrow that progresses quickly, making an overabundance of immature lymphocytes, a type of white blood cell. It is also the most common type of cancer among children, although it can also affect adults.
Of the 59 children treated with CTL019, 55 or 93 percent experienced complete remission, and 79 percent survived for one year following treatment. About three-quarters of the treated patients (76%) survived without relapse for 6 months, while more than half (55%) survived for a year without relapse. Of the 20 participants who experienced a relapse, 13 developed CD19-negative cells, which do not respond to CTL019 treatments, while 3 participants relapsed even after additional treatments.
The test of CTL019 with acute lymphoblastic leukemia is a follow-up to an earlier study with 30 children and adults with the disease. Those findings, reported by Science & Enterprise, also showed high initial remission rates and most participants experiencing 6 to 12 months of relapse-free survival.
The second trial tested CTL019 treatments in adult patients with non-Hodgkin lymphoma, a cancer of lymph tissue that forms part of the body’s immune system. There are different types of non-Hodgkin lymphoma reflecting different types of white blood cells. Most adults with the disorder have either diffuse large B-cell lymphoma, which is usually aggressive, and follicular lymphoma, a slower growing cancer.
This study, led by Stephen Schuster who heads Penn’s lymphoma research program, found more than half (57%) of the 28 participants responding to CTL019 treatments within 3 months following their infusions. Participants had non-Hodgkin lymphoma that did not respond to conventional therapies, including stem cell transplants. Response rates were higher in patients with follicular lymphoma (72%) than diffuse large B cell lymphoma (47%). After nearly 12 months, progression-free survival was 62 percent for those responding to CTL019 treatments, with all (100%) of responding follicular lymphoma patients surviving.
Many of the participants in both studies — 50 of the 53 children and 16 of 28 adults — experienced cytokine release syndrome from the treatments. Cytokine release syndrome occurs when enzymes are emitted from cells targeted by treatments, which can cause flu-like symptoms such as fevers, nausea, and muscle pain, but also neurological symptoms including hallucinations and delirium. The researchers say all participants experiencing these conditions recovered, but one lymphoma patient developed severe encephalitis several months after receiving the transplanted cells.
As reported by Science & Enterprise, Novartis and Penn began collaborating on chimeric antigen receptor therapies in 2012. Novartis received an exclusive license to treatments developed under the collaboration, and the company provides Penn with research funding and milestone payments for the achievement of clinical, regulatory, and commercial milestones, as well as royalty payments. In July 2014, CTL019 received breakthrough therapy status from the Food and Drug Administration.
Read more:
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- Eli Lilly Expanding NYC Labs for Cancer Therapies
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- Virus Particles Rebuilt to Boost Immunotherapies
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