T Cell Resistance to TGF-Beta in Lymphoma

Catherine Bollard, MBChB, MD, Professor of Pediatrics, Medicine, and Pathology & Immunology, Center for Cell and Gene Therapy, Texas Childrens Cancer Center, Baylor College of Medicine, discusses T cells and TGF-beta in Hodgkin's lymphoma and non-Hodgkin lymphoma.

In a study looking at LMP-specific T cells, 13 of 21 patients went into complete or partial remission, Bollard says, leaving 8 patients who did not respond to therapy. Researchers determined that there was a need for more potent T cells.

TGF-beta is secreted by most human cancers, in particular Hodgkin's lymphoma and non-Hodgkin lymphoma, and has devastating effects on T cell proliferation and function in vivo. Bollard says that the goal of ongoing research is to genetically modify LMP-specific T cells to be resistant to TGF-beta. If these T cells become resistant, they will not be killed by TGF-beta in the tumor microenvironment and can effectively kill the tumor.

Clinical Pearls

Seven patients have been treated with genetically-modified TGF-beta-resistant T cells and all have responded. Though these data are encouraging, Bollard says, it's still early to draw any conclusions. TGF-beta-resistant T cells are also being explored in melanoma, lung cancer, and brain tumors.

• TGF-beta is secreted by most human cancers, in particular Hodgkin's lymphoma and Non-Hodgkin lymphoma
• TGF-beta has devastating effects on T cell proliferation and function in vivo
• Research is being conducted to genetically modify LMP-specific T cells to be resistant to TGF-beta