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According to Medical Xpress
Hodgkin lymphoma, nodular lymphocyte predominant (high-power view) Credit: Gabriel Caponetti, MD./Wikipedia/CC BY-SA 3.0
In a first-of-its-kind clinical study, Baylor College of Medicine evaluated the safety, survival and anti-tumor activity of tumor-specific T cells rendered resistant to transforming growth factor β (TGFβ), in patients with Epstein Barr Virus (EBV) positive lymphoma. The results appear in the Journal of Clinical Oncology.
T cell therapies have demonstrated encouraging results and benefits in patients with chemotherapy resistant lymphoma, but despite these advances, a large number of patients still respond poorly. A major advantage of T cell therapy is that it is highly targeted to tumor cells, so it does not cause bystander damage. Patients can have successful responses with virtually no toxicity, unlike their experience with chemotherapy and radiation.
Like most tumors, lymphomas are immunosuppressive and contain multiple cell types that secrete inhibitory molecules, including TGFβ. TGFβ inhibits the expansion and function of tumor-directed T cells, limiting their ability to eliminate tumors.
“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,” said Dr. Cliona Rooney, professor of pediatrics, division of hematology and oncology and the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital.
The research team began to investigate this strategy in 2002. Early studies showed that T cells expressing the dominant-negative TGFβ receptor could grow in the presence of TGFβ, while unmodified T cells failed to grow and died within two weeks. Later, they evaluated the strategy in animal models for safety and efficacy, which led to the design of the clinical trial…
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