Summary: After years of effort, this revolutionary gene-modified T cell therapy is bearing fruit in treating a type of lymphoma, a resistant form of cancer. [This article first appeared on the website LongevityFacts.com. Author: Brady Hartman. ]
Thirty-seven-year-old Nick Asoian of Denver unsuccessfully fought Hodgkin’s Lymphoma using conventional cancer treatments for two years. In 2008, while in New Zealand for a ski race, Nick was diagnosed with Hodgkin’s Lymphoma. Two bone marrow transplants and two years of chemotherapy combined with radiation therapy didn’t bring his cancer to heel.
Then, a few years ago the avid skier got wind of clinical trial using T cell therapy at the Center for Cell and Gene Therapy at the Baylor College of Medicine in Texas. After speaking with Dr. Bollard and Vicky Torrano, the physicians conducting the trial, Asoian decided to give it a shot.
A Brother’s Help
Nick underwent 12 treatments over the course of 2 years, which consisted of taking his brother Nate’s blood and extracting the T cells. Technicians then engineered those cells to be resistant to the toxin emitted by the Hodgkin’s disease.
After two years using the novel T cell therapy, the results have been nothing short of remarkable.
“Over the course of about two years I had 12 infusions, and since my last infusion I have had many PET scans that are now showing no evidence of Hodgkin’s disease.” said Asoian.
First-of-Its-Kind Trial for T Cell Therapy
In a first-of-its-kind clinical trial, Baylor College of Medicine (BCM) evaluated the safety, survival and anti-tumor activity of tumor-targeted T cells in patients with a type of cancer known as Epstein Barr Virus (EBV) positive lymphoma. The researchers published their results in the Journal of Clinical Oncology.
T cell therapy has shown promise, benefitting patients with chemotherapy-resistant lymphoma. Despite these advances, however, a large number of patients still respond poorly.
Lymphoma is the type of cancer that begins in the lymphocytes – the infection-fighting cells of the immune system. Lymphocytes are in the bone marrow, lymph nodes, spleen, thymus and other parts of the body. In the disease of lymphoma, the lymphocytes change and grow out of control.
The primary advantage of T cell therapy is that it does not cause bystander damage because it is highly targeted to tumor cells. Patients have had successful responses with virtually no toxicity, unlike the experience with conventional cancer treatments such as radiation and chemotherapy.
Like most tumors, lymphomas suppressive the immune system by secreting immune-system inhibitory chemicals. One of these inhibitory molecules called TGFβ, inhibits the expansion and function of tumor-fighting T cells, limiting their ability to eradicate tumors.
The research team said this work exemplifies bench-to-bedside efforts and the power of virus-specific T cells to produce a significant patient response with little toxicity.
Dr. Cliona Rooney is the senior author of the study and a professor of pediatrics, in the division of hematology and oncology and the Baylor College of Medicine, the Texas Children’s Hospital, and the Houston Methodist Hospital. Dr. Rooney described the treatment, saying
“We modified our EBV-specific T cells with a dominant-negative TGFβ receptor in which the intracellular signaling domain had been deleted. This mutant receptor can bind TGFβ but does not transmit an inhibitory signal and also blocks the inhibitory signaling of TGFβ through its normal receptor”
Origins of the T Cell Therapy
The research team began to investigate this type of T cell therapy in 2002. Earlier studies showed that T cells expressing the dominant-negative TGFβ receptor could grow in the presence of TGFβ, while unmodified T cells failed to develop and died within two weeks. Later, the team evaluated the safety and efficacy of the strategy using animal models. The success of the T cell therapy in animal experiments led to the clinical trial. As Dr. Rooney says,
“In an earlier clinical study of unmodified EBV-specific T cells, more than 50 percent of patients experienced complete remission, and tumor responses were observed in over 70 percent,” Dr. Rooney added, “In the new study, patients who did not experience complete responses to unmodified EBVSTs had complete responses to the same T cells modified with the dominant negative TGFb receptor.”
Dr. Bollard is the first author of the study and director of the Children’s Research Institute’s Center for Cancer & Immunology Research and was at Baylor when the study was conducted. Dr. Bollard says the results hold promise, adding
“These results come 18 years after this revolutionary approach was first conceptualized. While the study is small, its findings are encouraging for our patients’ families and for the cancer field.”
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References / Additional Reading
Cover photo: Modifying genes for T Cell Therapy. Credit: National Institutes of Health.
Hartman, B. “Can We Restore Thymus Function to Cheat Death?” Web. November 22, 2017. Link to article.
“Gene-modified, virus-specific T cell therapy shows promise in treating lymphoma, with little toxicity.” Baylor College of Medicine. Jan 25, 2018 [BCM Press Release].
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